Tetrahydropyridothiophenes

ABSTRACT

Compounds of a certain formula (I) 
                         
in which Ra and Rb have the meanings indicated in the description, are novel, effective compounds with anti-proliferative and/or apoptosis inducing activity.

This application was filed under 35 U. S. C. 371 as a national stage ofPCT/EP2005/052384, filed May 25, 2005.

FIELD OF APPLICATION OF THE INVENTION

The invention relates to tetrahydropyridothiophene derivatives, whichcan be used in the pharmaceutical industry for the production ofpharmaceutical compositions.

The invention further relates to the contribution made to the art by thefinding, that said tetrahydropyridothiophene derivatives displaycell-cycle dependent, anti-proliferative and apoptosis inducingactivity.

The invention also relates to the use of these compounds for the therapyof hyperproliferative diseases, in particular human cancer.

KNOWN TECHNICAL BACKGROUND

Cancer chemotherapy was established with the alkylating agentCyclophosphamide (Endoxan®), an oxazaphosphorine pro-drug activatedpreferentially in the tumor. The target of alkylating agents likeCyclophosphamide is DNA and the concept, that cancer cells withuncontrolled proliferation and a high mitotic index are killedpreferentially, proved to be very successful. Standard cancerchemotherapeutic drugs finally kill cancer cells upon induction ofprogrammed cell death (“apoptosis”) by targeting basic cellularprocesses and molecules. These basic cellular processes and moleculesinclude RNA/DNA (alkylating and carbamoylating agents, platin analogsand topoisomerase inhibitors), metabolism (drugs of this class are namedanti-metabolites and examples are folic acid, purin and pyrimidineantagonist) as well as the mitotic spindle apparatus with αβ-tubulinheterodimers as the essential component (drugs are categorized intostabilizing and destabilizing tubulin inhibitors; examples areTaxol/Paclitaxel®, Docetaxel/Taxotere® and vinca alkaloids).

A subgroup of proapoptotic anticancer agents target cells preferentiallyin mitosis. In general these agents do not induce apoptosis innon-dividing cells, arrested in the G0, G1 or G2 phase of the celldivision cycle. In contrast, dividing cells going through mitosis(M-phase of the cell division cycle), are killed efficiently byinduction of apoptosis by this subgroup agents. Therefore, this subgroupor class of anti-cancer agents is described as cell-cycle specific orcell-cycle dependent. Tubulin inhibitors, with Taxol (Paclitaxel®) as aprominent example, belong to this class of cell-cycle specific,apoptosis inducing anti-cancer agents.

PRIOR ART

The international application WO2004/024065 describes, inter alia,tetrahydropyridothiophene derivatives as glucagons antagonists for thetreatment of diabetes.

The german document DE4039734 describes, inter alia, N-alkylatedtetrahydropyridothiophene derivatives as components of herbicidalagents.

The german document DD272078 describes, inter alia, N-alkylatedtetrahydropyridothiophene derivatives with antianaphylactic undantihistaminergic properties.

The international application WO98/02440 describes3-ureido-pyridothiophens which can be used for the treatment of acuteand chronic inflammatory processes.

The Ambinter Screening Library discloses certaintetrahydropyridothiophens which differ profoundly from the compoundsaccording to the present invention.

The international application WO2005/033102 describes thiophene-basedcompounds exhibiting ATP-utilizing enzyme inhibitory activity.

DESCRIPTION OF THE INVENTION

It has now been found that the tetrahydropyridothiophene derivatives,which are described in greater details below, differ from prior artcompounds by creative structural alterations and have surprising andparticularly advantageous properties.

In more detail, it has been unexpectedly found thattetrahydropyridothiophene derivatives, which are described in greaterdetails below, are potent and highly efficacious inhibitors of cellular(hyper)proliferation and/or cell-cycle specific inducers of apoptosis incancer cells. Therefore, unanticipatedly, thesetetrahydropyridothiophene derivatives can be useful for treating(hyper)proliferative diseases and/or disorders responsive to theinduction of apoptosis, in particular cancer. By having a cell-cyclespecific mode of action, tetrahydropyridothiophene derivates accordingto this invention should have a higher therapeutic index compared tostandard chemotherapeutic drugs targeting basic cellular processes likeDNA replication or interfering with basic cellular molecules like DNA.

Thus, for example, the compounds according to this invention areexpected to be useful in targeted cancer therapy.

The invention thus relates in a first aspect (aspect 1) to compounds offormula I

wherein

-   Ra is —C(O)R1, —C(O)OR2, —C(O)SR2, —C(O)N(R3)R4, —S(O)₂R1, or    —S(O)₂N(R3)R4;-   Rb is Q-2-4C-alkenyl, in which    either-   Q is optionally substituted by Rba and/or Rbb and/or Rbc, and is    phenyl or naphthyl,    or-   Q is optionally substituted by Rca and/or Rcb, and is Har,    or-   Q is Cyc;    in which-   R1, R2 and R3 may be the same or different and are independently    selected from the group consisting of: hydrogen, 1-7C-alkyl,    3-7C-cycloalkyl, Ar, Har and Het, wherein each of said 1-7C-alkyl,    3-7C-cycloalkyl, Ar, Har and Het can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R5;-   each R4 is independently selected from the group consisting of:    hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl, wherein each of said    1-7C-alkyl and 3-7C-cycloalkyl can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R5;-   R5, Rba, Rbb, Rbc, Rca and Rcb may be the same or different and are    independently selected from the group consisting of:    -   1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har, Het,    -   halogen, trifluoromethyl, nitro, cyano, guanidino, amidino,    -   —C(O)R6, —C(O)OR7, —C(O)N(R8)R9, —S(O)₂R6, —S(O)₂N(R8)R9,    -   —N(R10)C(O)R6, —N(R10)C(O)OR7, —N(R10)C(O)N(R8)R9,        —N(R10)S(O)₂R6,    -   —N(R10)S(O)₂N(R8)R9,    -   —OC(O)R6, —OC(O)N(R8)R9,    -   —OR7, —N(R8)R9 and —SR7, wherein each of said 1-7C-alkyl,        3-7C-cycloalkyl, Ar, Har and Het can be unsubstituted or        optionally substituted by at least one substituent independently        selected from R11;-   R6, R7 and R8 may be the same or different and are independently    selected from the group consisting of: hydrogen, 1-7C-alkyl,    3-7C-cycloalkyl, Ar, Har and Het, wherein each of said 1-7C-alkyl,    3-7C-cycloalkyl, Ar, Har and Het can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R12;-   each R9 is independently selected from the group consisting of:    hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl, wherein each of said    1-7C-alkyl and 3-7C-cycloalkyl can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R12;-   each R10 is independently selected from the group consisting of:    hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl;-   R11 is selected from the group consisting of: R5 as defined above;-   each R12 is independently selected from the group consisting of: R5    as defined above;-   each Ar is independently selected from phenyl and naphthyl;-   each Har is independently any fully aromatic or partially aromatic    mono- or fused bicyclic ring or ring system made up of-   a first constituent being a 5- or 6-membered monocyclic unsaturated,    aromatic heteroaryl ring A, which heteroaryl ring A comprises one to    four heteroatoms independently selected from nitrogen, oxygen and    sulfur,-   and, optionally, fused to said first constituent,-   a second constituent being a benzo group, any 3-7C-cycloalkane group    as defined herein, any additional heteroaryl ring A as defined    herein, or any heterocyclic ring B as defined herein,-   whereby said Har ring or ring system is attached to the parent    molecular group via a substitutable ring carbon or ring nitrogen    atom;-   each Het is independently any fully saturated or partially    unsaturated mono- or fused bicyclic ring or ring system made up of-   a first constituent being a 3- to 7-membered monocyclic fully    saturated or partially unsaturated, non-aromatic heterocyclic ring    B,    -   which heterocyclic ring B comprises one to three heteroatoms        independently selected from nitrogen, oxygen and sulfur,    -   and which heterocyclic ring B is optionally substituted by one        or two oxo groups,-   and, optionally, fused to said first constituent,-   a second constituent being a benzo group, any 3-7C-cycloalkane group    as defined herein, or any additional heterocyclic ring B as defined    herein,-   whereby said Het ring or ring system is attached to the parent    molecular group via a substitutable ring carbon or ring nitrogen    atom;

Cyc is optionally substituted by halogen on its benzene ring, and is agroup of formula A

in which

-   G is optionally substituted by Rda and/or Rdb, and is a 5- or    6-membered saturated heterocyclic ring comprising one or two    heteroatoms independently selected from the group consisting of    nitrogen, oxygen and sulfur, in which-   Rda is 1-4C-alkyl or halogen,-   Rdb is 1-4C-alkyl or halogen,-   whereby said Cyc ring system is attached to the parent molecular    group via a substitutable benzoring carbon atom;    and the salts, solvates or the solvates of the salts thereof.

The invention further relates in a second aspect (aspect 2), which is anembodiment of aspect 1, to compounds of formula I

wherein

-   Ra is —C(O)R1, —C(O)OR2, —C(O)SR2, —C(O)N(R3)R4, —S(O)₂R1, or    —S(O)₂N(R3)R4;-   Rb is Q-2-4C-alkenyl, in which    either-   Q is optionally substituted by Rba and/or Rbb and/or Rbc, and is    phenyl or naphthyl,    or-   Q is optionally substituted by Rca and/or Rcb, and is Har,    or-   Q is Cyc;    in which-   R1, R2 and R3 may be the same or different and are independently    selected from the group consisting of: hydrogen, 1-7C-alkyl,    3-7C-cycloalkyl, Ar, Har and Het, wherein each of said 1-7C-alkyl,    3-7C-cycloalkyl, Ar, Har and Het can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R5;-   each R4 is independently selected from the group consisting of:    hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl, wherein each of said    1-7C-alkyl and 3-7C-cycloalkyl can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R5;-   R5, Rba, Rbb, Rbc, Rca and Rcb may be the same or different and are    independently selected from the group consisting of:    -   1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har, Het,    -   halogen, trifluoromethyl, nitro, cyano, guanidino, amidino,    -   —C(O)R6, —C(O)OR7, —C(O)N(R8)R9, —S(O)₂R6, —S(O)₂N(R8)R9,    -   —N(R10)C(O)R6, —N(R10)C(O)OR7, —N(R10)C(O)N(R8)R9,        —N(R10)S(O)₂R6,    -   —N(R10)S(O)₂N(R8)R9,    -   —OC(O)R6, —OC(O)N(R8)R9,    -   —OR7, —N(R8)R9 and —SR7, wherein each of said 1-7C-alkyl,        3-7C-cycloalkyl, Ar, Har and Het can be unsubstituted or        optionally substituted by at least one substituent independently        selected from R11;-   R6, R7 and R8 may be the same or different and are independently    selected from the group consisting of: hydrogen, 1-7C-alkyl,    3-7C-cycloalkyl, Ar, Har and Het, wherein each of said 1-7C-alkyl,    3-7C-cycloalkyl, Ar, Har and Het can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R12;-   each R9 is independently selected from the group consisting of:    hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl, wherein each of said    1-7C-alkyl and 3-7C-cycloalkyl can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R12;-   each R10 is independently selected from the group consisting of:    hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl;-   R11 is selected from the group consisting of: R5 as defined above;-   each R12 is independently selected from the group consisting of: R5    as defined above;-   each Ar is independently selected from phenyl and naphthyl;-   each Har is independently any fully aromatic or partially aromatic    mono- or fused bicyclic ring or ring system made up of-   a first constituent being a 5- or 6-membered monocyclic unsaturated,    aromatic heteroaryl ring A, which heteroaryl ring A comprises one to    four heteroatoms independently selected from nitrogen, oxygen and    sulfur,-   and, optionally, fused to said first constituent,-   a second constituent being a benzo group, any 3-7C-cycloalkane group    as defined herein, any additional heteroaryl ring A as defined    herein, or any heterocyclic ring B as defined herein,-   whereby said Har ring or ring system is attached to the parent    molecular group via a substitutable ring carbon or ring nitrogen    atom;-   each Het is independently any fully saturated or partially    unsaturated mono- or fused bicyclic ring or ring system made up of-   a first constituent being a 3- to 7-membered monocyclic fully    saturated or partially unsaturated, non-aromatic heterocyclic ring    B,    -   which heterocyclic ring B comprises one to three heteroatoms        independently selected from nitrogen, oxygen and sulfur,    -   and which heterocyclic ring B is optionally substituted by one        or two oxo groups,-   and, optionally, fused to said first constituent,-   a second constituent being a benzo group, any 3-7C-cycloalkane group    as defined herein, or any additional heterocyclic ring B as defined    herein,-   whereby said Het ring or ring system is attached to the parent    molecular group via a substitutable ring carbon or ring nitrogen    atom;-   Cyc is a group of formula A

in which

-   G is a 5- or 6-membered saturated heterocyclic ring comprising one    or two heteroatoms independently selected from the group consisting    of nitrogen, oxygen and sulfur,-   whereby said Cyc ring system is attached to the parent molecular    group via a substitutable benzoring carbon atom;    and the salts, solvates or the solvates of the salts thereof.

As used herein, “alkyl” refers to both branched and straight chainsaturated aliphatic hydrocarbon groups having the specified numbers ofcarbon atoms, such as for example:

-   1-4C-Alkyl is a straight-chain or branched alkyl radical having 1 to    4 carbon atoms. Examples are the butyl, isobutyl, sec-butyl,    tert-butyl, propyl, isopropyl, and, particularly, the ethyl and    methyl radicals.-   1-7C-Alkyl is a straight-chain or branched alkyl radical having 1 to    7 carbon atoms. Examples are the heptyl, isoheptyl (5-methylhexyl),    hexyl, isohexyl (4-methylpentyl), neohexyl (3,3-dimethylbutyl),    pentyl, isopentyl (3-methylbutyl), neopentyl (2,2-dimethylpropyl),    butyl, isobutyl, sec-butyl, tert-butyl, isopropyl, and, in    particular, the propyl, ethyl and methyl radicals, in more    particular the ethyl and methyl radicals.-   1-7C-Alkyl, which is substituted as described herein, refers to one    of the abovementioned 1-7C-alkyl radicals, which is substituted as    described herein, and may include for example, without being    restricted thereto, propyl, ethyl or methyl.

One notable embodiment of herein-mentioned “alkyl” having the specifiednumbers of carbon atoms refers to the straight-chain radicals thereof.Thus, for example, a notable embodiment of 1-7C-alkyl, 1-6C-alkyl or1-5C-alkyl as mentioned herein refers to straight-chain 1-5C-alkylradicals, especially to straight-chain 1-4C-alkyl radicals, such as e.g.the methyl, ethyl, propyl, butyl or pentyl radical.

-   2-4C-Alkenyl is a straight chain or branched alkenyl radical having    2 to 4 carbon atoms. Examples are the 2-butenyl, 3-butenyl,    isopropenyl, 1-propenyl, 2-propenyl(allyl) and, particularly, the    ethenyl (vinyl) radical, as well as all possible stereoisomers    thereof.-   Q-2-4C-alkenyl stands for one of the abovementioned 2-4C-alkenyl    radicals substituted by the moiety Q, which has the meanings as    given herein. Exemplarily may be preferably mentioned the    2-Q-ethen-1-yl radical [—CH═CH-Q], which stands for an ethenyl    radical substituted in 2-position by the moiety Q, particularly the    trans isomer thereof. As further example, the    2-Q-(1-methyl)-ethen-1-yl radical [—C(CH₃)═CH-Q] may be mentioned.-   3-7C-Cycloalkyl stands for cyclopropyl, cyclobutyl, cyclopentyl,    cyclohexyl and cycloheptyl, of which cyclopropyl and cyclopentyl are    to be emphasized.-   3-7C-Cycloalkane stands for cyclopropane, cyclobutane, cyclopentane,    cyclohexane and cycloheptane, of which cyclohexane and cyclopentane    are to be emphasized.

Halogen within the meaning of the present invention is iodine, or,particularly, bromine, chlorine and fluorine.

-   1-4C-Alkoxy represents radicals which, in addition to the oxygen    atom, contain a straight-chain or branched alkyl radical having 1 to    4 carbon atoms. Examples which may be mentioned are the butoxy,    isobutoxy, sec-butoxy, tert-butoxy, propoxy, isopropoxy and    preferably the ethoxy and methoxy radicals.-   2-4C-Alkoxy represents radicals which, in addition to the oxygen    atom, contain a straight-chain or branched alkyl radical having 2 to    4 carbon atoms. Examples which may be mentioned are the butoxy,    isobutoxy, sec-butoxy, tert-butoxy, propoxy, isopropoxy and    preferably the ethoxy radical.-   1-4C-Alkoxy-2-4C-alkoxy stands for a 2-4C-alkoxy radical which is    substituted by one of the abovementioned 1-4C-alkoxy radicals.    Examples which may be mentioned are the 2-(methoxy)ethoxy    (—O—CH₂—CH₂—O—CH₃) and the 2-(ethoxy)ethoxy radical    (—O—CH₂—CH₂—O—CH₂—CH₃).-   Phenyl-1-4C-alkoxy represents one of the abovementioned 1-4C-alkoxy    radicals, which is substituted by a phenyl radical. Examples which    may be mentioned are the phenethoxy and the benzyloxy radicals.-   1-4C-Alkylcarbonyl represents a radical which, in addition to the    carbonyl group, contains one of the abovementioned 1-4C-alkyl    radicals. An example which may be mentioned is the acetyl radical.-   1-4C-Alkoxycarbonyl represents a radical which, in addition to the    carbonyl group, contains one of the abovementioned 1-4C-alkoxy    radicals. Examples which may be mentioned are the methoxycarbonyl,    the ethoxycarbonyl and the tertbutoxycarbonyl radicals.-   1-4C-Alkylcarbonyloxy radicals contain, in addition to the oxygen    atom, one of the abovementioned 1-4C-alkylcarbonyl radicals. An    example is the acetoxy radical (CH₃C(O)—O—).

In addition to the nitrogen atom, mono- or di-1-4C-alkylamino radicalscontain one or two of the abovementioned 1-4C-alkyl radicals.Di-1-4C-alkylamino is preferred and here, in particular, dimethyl-,diethyl- or diisopropylamino.

-   Mono- or Di-1-4C-alkylaminocarbonyl radicals contain in addition to    the carbonyl group one of the abovementioned mono- or    di-1-4C-alkylamino radicals. Examples which may be mentioned are the    N-methyl- the N,N-dimethyl-, the N-ethyl-, the N-propyl-, the    N,N-diethyl- and the N-isopropylaminocarbonyl radical.-   An 1-4C-Alkylcarbonylamino radical is, for example, the    propionylamino (C₃H₇C(O)NH—) and the acetylamino radical    (CH₃C(O)NH—).-   Phenyl-1-4C-alkyl represents one of the abovementioned 1-4C-alkyl    radicals, which is substituted by a phenyl radical. Examples which    may be mentioned are the phenethyl and the benzyl radicals.-   (1-4C-Alkoxy)-phenyl stands for a phenyl radical which is    substituted by one of the abovementioned 1-4C-alkoxy radicals.-   Di-(1-4C-alkoxy)-phenyl stands for a phenyl radical which is    substituted by two of the abovementioned 1-4C-alkoxy radicals.-   Ar stands for naphthyl or, particularly, phenyl.

As completely or predominantly fluorine-substituted 1-4C-alkoxy, forexample, the 2,2,3,3,3-penta-fluoropropoxy, the perfluoroethoxy, the1,2,2-trifluoroethoxy, in particular the 1,1,2,2-tetrafluoroethoxy, the2,2,2-trifluoroethoxy, the trifluoromethoxy and preferably thedifluoromethoxy radicals may be mentioned. “Predominantly” in thisconnection means that more than half of the hydrogen atoms of the1-4C-alkoxy radicals are replaced by fluorine atoms.

-   Pyridyl-1-4C-alkoxy represents one of the abovementioned 1-4C-alkoxy    radicals, which is substituted by a pyridyl radical. Examples which    may be mentioned are the 2-pyridyl-ethoxy and the pyridylmethoxy    radicals.-   Pyridyl includes pyridin-2-yl, pyridin-3-yl and pyridin-4-yl.

As it is known for the skilled person, the terms imidazolo, pyrazolo,piperidino or morpholino stands for imidazol-1-yl, pyrazol-1-yl,piperidin-1-yl or morpholin-4-yl, respectively. Similar terms usedherein are to be understood similarly, mutatis mutandis, as defined forthese terms.

-   (1-4C-Alkoxy-2-4C-alkoxy)-2-4C-alkoxy represents 2-4C-alkoxy    radicals, which are substituted by one of the abovementioned    1-4C-alkoxy-2-4C-alkoxy radicals. Examples which may be mentioned    are the 2-(2-methoxyethoxy)-ethoxy and the 2-(2-ethoxyethoxy)-ethoxy    radicals.-   Hydroxy-2-4C-alkoxy represents 2-4C-alkoxy radicals, which are    substituted by a hydroxyl group. Examples which may be mentioned are    the 2-hydroxyethoxy and the 3-hydroxypropoxy radicals.-   3-7C-Cycloalkyl-1-4C-alkoxy stands for one of the abovementioned    1-4C-alkoxy radicals substituted by one of the abovementioned    3-7C-cycloalkyl radicals. Examples which may be mentioned are the    3-7C-cycloalkylmethoxy radicals, such as cyclopropylmethoxy,    cyclobutylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy or    cycloheptylmethoxy, of which cyclopropylmethoxy, cyclobutylmethoxy    or cyclopentylmethoxy are in particular to be mentioned.-   3-7C-Cycloalkoxy stands for cyclopropyloxy, cyclobutyloxy,    cyclopentyloxy, cyclohexyloxy or cycloheptyloxy, of which    cyclopropyloxy, cyclobutyloxy and cyclopentyloxy are to be    emphasized.-   Cyano-1-4C-alkoxy represents 1-4C-alkoxy radicals, which are    substituted by one cyano radical. Examples which may be mentioned    are the cyanomethoxy and the 2-cyanoyethoxy radicals.

The expression (Rba)-phenyl means that the phenyl radical is substitutedby Rba, which is attached to any of the positions of the phenyl ring;the expression 2-(Rba)-phenyl means that the phenyl radical issubstituted by Rba, which is attached in the 2-position to the phenylradical (i.e. the ortho position with respect to the binding position inwhich the phenyl ring is bonded to the parent molecular group); theexpression “Rbb-substituted 2-(Rba)-phenyl” means that the phenylradical is substituted by both Rbb and Rba, whereby the substituent Rbais bonded in the 2-position to the phenyl radical, and the substituentRbb is bonded in any other position to the phenyl ring; and theexpression “2-(Rba)-5-(Rbb)-phenyl” means, that the phenyl radical issubstituted by both Rba and Rbb, whereby the substituent Rba is bondedin the 2-position to the phenyl radical, and the substituent Rbb isbonded in the 5-position to the phenyl ring; In this connection, furthersimilar expressions mentioned herein indicating in short form thepositions in which substituents are bonded to a ring radical are to beunderstood similarly, mutatis mutandis, as specified exemplarily andrepresentatively for the foregoing expressions.

The term (R5)-methyl stand for methyl which is substituted by R5. Theterm 2-(R5)-ethyl stands for ethyl which is substituted in 2-position byR5. The term 3-(R5)-propyl stands for propyl which is substituted in3-position by R5.

Har stands for a fully aromatic or partially aromatic mono- or fusedbicyclic ring or ring system made up of

-   a first constituent being a 5- or 6-membered monocyclic unsaturated,    aromatic heteroaryl ring A, which heteroaryl ring A comprises one to    four heteroatoms independently selected from nitrogen, oxygen and    sulfur,-   and, optionally, fused to said first constituent,-   a second constituent being a benzo group, a 3-7C-cycloalkane group    as defined herein, an additional heteroaryl ring A as defined    herein, or a heterocyclic ring B as defined herein,    whereby said Har ring or ring system is attached to the parent    molecular group via a substitutable ring carbon or ring nitrogen    atom of any of said constituents.

Examples for Har may include, but are not limited to, 5-memberedheteroaryl radicals, such as e.g. furanyl, thiophenyl, pyrrolyl,oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl,triazolyl, thiadiazolyl, oxadiazolyl, and 6-membered heteroarylradicals, such as e.g. pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl,

-   and the benzo-fused derivatives thereof such as e.g. quinazolinyl,    quinoxalinyl, cinnolinyl, quinolinyl, isoquinolinyl, indolyl,    isoindolyl, indazolyl, phthalazinyl, benzothiophenyl, benzofuranyl,    isobenzofuranyl, benzoxazolyl, benzothiazolyl, benzimidazolyl,    benzotriazolyl, benzoxadiazolyl or benzothiadiazolyl,    as well as naphthyridinyl, indolizinyl or purinyl.

Het stands for a fully saturated or partially unsaturated mono- or fusedbicyclic ring or ring system made up of

-   a first constituent being a 3- to 7-membered monocyclic fully    saturated or partially unsaturated, non-aromatic heterocyclic ring    B,    -   which heterocyclic ring B comprises one to three heteroatoms        independently selected from nitrogen, oxygen and sulfur,    -   and which heterocyclic ring B is optionally substituted by one        or two oxo groups,-   and, optionally, fused to said first constituent,-   a second constituent being a benzo group, a 3-7C-cycloalkane group    as defined herein, or an additional heterocyclic ring B as defined    herein,-   whereby said Het ring or ring system is attached to the parent    molecular group via a substitutable ring carbon or ring nitrogen    atom of any of said constituents.

Examples for Het may include, but are not limited to, aziridinyl,azetidinyl, pyrrolidinyl, piperidinyl, homopiperidinyl, pyrazolidinyl,imidazolidinyl, piperazinyl, homopiperazinyl, morpholinyl orthiomorpholinyl,

-   and the partially unsaturated derivatives thereof such as e.g.    pyrrolinyl, imidazolinyl or pyrazolinyl, and the oxo substituted    derivatives of the aforementioned examples such as e.g.    2-oxopyrrolidinyl, 2-oxoimidazolidinyl, 2-oxopiperidinyl,    2,5-dioxopyrrolidinyl, 2,5-dioxoimidazolidinyl,    2,6-dioxopiperidinyl, 2-oxopiperazinyl or 5-oxo-1,4-diazepanyl, or    S-oxo-thiomorpholinyl or S,S-dioxo-thiomorpholinyl, and the    benzo-fused derivatives of the aforementioned examples such as e.g.    indolinyl, isoindolinyl, 1,2,3,4-tetrahydroquinolinyl or    1,2,3,4-tetrahydroisoquinolinyl,-   as well as 1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl,    2,3-dihydrobenzothiophenyl, chromenyl, chromanyl, or    2,3-dihydrobenzofuranyl.

More detailed exemplary Het radicals include those isomers of theabovementioned examples which are attached via a ring nitrogen atom,such as e.g., without being limited to, aziridin-1-yl, azetidin-1-yl,pyrrolidin-1-yl, piperidin-1-yl, homopiperidin-1-yl, piperazin-1-ylhomopiperazin-1-yl, morpholin-4-yl or thiomorpholin-4-yl, orS-oxo-thiomorpholin-4-yl or S,S-dioxo-thiomorpholin-4-yl.

Other more detailed exemplary Het radicals include those isomers of theabovementioned examples which are attached via a ring carbon atom, suchas e.g., without being limited to, pyrrolidin-2-yl, pyrrolidin-2-yl,piperidin-2-yl, piperidin-3-yl, piperidin-4-yl or piperazin-2-yl.

As used herein, the term “oxo” forms a carbonyl moiety when attached ata carbon atom, a sulfoxide moiety when attached to a sulfur atom and asulfonyl moiety when two of said terms are attached to a sulfur atom.

In a first embodiment, Cyc is optionally substituted by halogen on itsbenzene ring, and is a group of formula A

in which

-   G is optionally substituted by Rda and/or Rdb, and is a 5- or    6-membered saturated heterocyclic ring comprising one or two    heteroatoms independently selected from the group consisting of    nitrogen, oxygen and sulfur, in which-   Rda is 1-4C-alkyl or halogen,-   Rdb is 1-4C-alkyl or halogen,    whereby said Cyc ring system is attached to the parent molecular    group via a substitutable benzoring carbon atom.

In a second embodiment Cyc is a group of formula A

in which

-   G is a 5- or 6-membered saturated heterocyclic ring comprising one    or two heteroatoms independently selected from the group consisting    of nitrogen, oxygen and sulfur,    whereby said Cyc ring system is attached to the parent molecular    group via any substitutable carbon atom of the benzene ring.

As examples of Cyc may be mentioned indolinyl, isoindolinyl,1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl,1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl,2,3-dihydrobenzothiophenyl, or 2,3-dihydrobenzofuranyl.

More detailed exemplary Cyc radicals include, without being limitedthereto, 1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl, chromenyl,chromanyl or 2,3-dihydrobenzofuranyl, as well as2,2-difluoro-1,3-benzodioxolyl.

Illustratively, as exemplary suitable Cyc radicals may be mentioned,without being limited thereto, 1,3-benzodioxolyl,2,3-dihydro-1,4-benzodioxinyl, 2,3-dihydrobenzofuranyl, as well as2,2-difluoro-1,3-benzodioxolyl.

As more specific exemplary suitable Cyc radicals may be mentioned,without being limited thereto, 1,3-benzodioxol-4-yl,1,3-benzodioxol-5-yl, 2,3-dihydro-1,4-benzodioxin-5-yl,2,3-dihydro-1,4-benzodioxin-6-yl, 2,3-dihydrobenzofuran-7-yl, as well as2,2-difluoro-1,3-benzodioxol-4-yl.

It is to be stated that Cyc is an embodiment of Het as defined herein.

In general, unless otherwise mentioned, the terms “Har”, “Het” and “Cyc”include all the possible isomeric forms thereof, particularly thepositional isomers thereof. Thus, for example, the term pyridyl orpyridinyl includes pyridin-2-yl, pyridin-3-yl and pyridin-4-yl.

Unless otherwise noted, constituents which are optionally substituted asstated herein, may be substituted by their substituents or parentmolecular groups at any possible position.

Notably, unless otherwise mentioned, the substituents Rba, Rbb and Rbcmay be attached at any possible position of the phenyl or naphthylradical.

Yet notably, unless otherwise mentioned, Ar may be substituted by itssubstituents or parent molecular groups at any possible position.

Still yet notably, unless otherwise mentioned, Har and Het may besubstituted by their substituents or parent molecular groups asmentioned herein at any possible position, such as e.g. at anysubstitutable ring carbon or ring nitrogen atom.

Further notable, in Q-2-4C-alkenyl, the Q moiety is substituted by the2-4C-alkenyl moiety at any possible position of the Q ring.

Thus e.g., in Har-2-4C-alkenyl, the Har moiety is substituted by the2-4C-alkenyl moiety at any possible position of the Har ring,particularly the Har moiety is substituted by the 2-4C-alkenyl moiety atany one of its ring carbon atoms. Likewise, in Cyc-2-4C-alkenyl, the Cycmoiety is substituted by the 2-4C-alkenyl moiety at any possibleposition of the benzo-moiety of Cyc.

Rings containing quaternizable imino-type ring nitrogen atoms (—N═) maybe preferably not substituted (i.e. quaternized) on these imino-typering nitrogen atoms by the mentioned substituents or parent moleculargroups.

Unless otherwise noted, any heteroatom of a heterocyclic ring withunsatisfied valences mentioned herein is assumed to have the hydrogenatom(s) to satisfy the valences.

When any variable occurs more than one time in any constituent, eachdefinition is independent.

The person skilled in the art is aware on account of his/her expertknowledge that certain combinations of the variable characteristicsmentioned in the description of this invention lead to chemically lessstable compounds. This can apply, for example, to certain compounds, inwhich—in a manner being disadvantageous for chemical stability—twoheteroatoms (S, N or O) would directly meet or would only be separatedby one carbon atom. This can also apply, for example, to certain freeacid derivatives, such as e.g. certain carbamic acid derivativescontaining a free carbamic acid function (N—C(O)OH). Those compoundsaccording to this invention, in which the combination of theabovementoned variable substituents does not lead to chemically lessstable compounds, are therefore preferred. Suitable salts for compoundsaccording to this invention—depending on substitution—are all acidaddition salts or all salts with bases. Particular mention may be madeof the pharmacologically tolerable inorganic and organic acids and basescustomarily used in pharmacy. Those suitable are, on the one hand,water-insoluble and, particularly, water-soluble acid addition saltswith acids such as, for example, hydrochloric acid, hydrobromic acid,phosphoric acid, nitric acid, sulphuric acid, acetic acid, citric acid,D-gluconic acid, benzoic acid, 2-(4-hydroxybenzoyl)benzoic acid, butyricacid, sulphosalicylic acid, maleic acid, lauric acid, malic acid,fumaric acid, succinic acid, oxalic acid, tartaric acid, embonic acid,stearic acid, toluenesulphonic acid, methanesulphonic acid or3-hydroxy-2-naphthoic acid, the acids being employed in saltpreparation—depending on whether a mono- or polybasic acid is concernedand depending on which salt is desired—in an equimolar quantitativeratio or one differing therefrom.

On the other hand, salts with bases are—depending on substitution—alsosuitable. As examples of salts with bases are mentioned the lithium,sodium, potassium, calcium, aluminium, magnesium, titanium, ammonium,meglumine or guanidinium salts, here, too, the bases being employed insalt preparation in an equimolar quantitative ratio or one differingtherefrom.

Pharmacologically intolerable salts, which can be obtained, for example,as process products during the preparation of the compounds according tothis invention on an industrial scale, are converted intopharmacologically tolerable salts by processes known to the personskilled in the art.

According to expert's knowledge the compounds according to thisinvention as well as their salts may contain, e.g. when isolated incrystalline form, varying amounts of solvents. Included within the scopeof the invention are therefore all solvates and in particular allhydrates of the compounds according to this invention as well as allsolvates and in particular all hydrates of the salts of the compoundsaccording to this invention.

In the context of this invention, hyperproliferation and analogous termsare used to describe aberrant/ dysregulated cellular growth, a hallmarkof diseases like cancer. This hyperproliferation might be caused bysingle or multiple cellular / molecular alterations in respective cellsand can be, in context of a whole organism, of benign or malignantbehaviour. Inhibition of cell proliferation and analogous terms is usedto denote an ability of the compound to retard the growth of a cellcontacted with that compound as compared to cells not contacted withthat compound. Most preferable this inhibition of cell proliferation is100%, meaning that proliferation of all cells is stopped and/or cellsundergo programmed cell death. In some preferred embodiments thecontacted cell is a neoplastic cell. A neoplastic cell is defined as acell with aberrant cell proliferation. A benign neoplasia is describedby hyperproliferation of cells, incapable of forming an aggressive,metastasizing tumor in-vivo. In contrast, a malignant neoplasia isdescribed by cells with different cellular and biochemicalabnormalities, capable of forming tumor metastasis. The acquiredfunctional abnormalities of malignant neoplastic cells (also defined as“hallmarks of cancer”) are replicative potential (“hyperproliferation”),self-sufficiency in growth signals, insensitivity to anti-growthsignals, evasion from apoptosis, sustained angiogenesis and issueinvasion and metastasis.

Inducer of apoptosis and analogous terms are used to identify a compoundwhich executes programmed cell death in cells contacted with thatcompound. Apoptosis is defined by complex biochemical events within thecontacted cell, such as the activation of cysteine specific proteinases(“caspases”) and the fragmentation of chromatin. Induction of apoptosisin cells contacted with the compound might not necessarily coupled withinhibition of cell proliferation. Preferably, the inhibition of cellproliferation and/or induction of apoptosis is specific to cells withaberrant cell growth (hyperproliferation). Thus, compared to cells withaberrant cell growth, normal proliferating or arrested cells are lesssensitive or even insensitive to the proliferation inhibiting orapoptosis inducing activity of the compound. Finally, cytotoxic is usedin a more general sense to identify compounds which kill cells byvarious mechanisms, including the induction of apoptosis/programmed celldeath in a cell cycle dependent or cell-cycle independent manner.

Cell cycle specific and analogous terms are used to identify a compoundas including apoptosis only in continuously proliferating cells activelypassing a specific phase of the cell cycle, but not in resting,non-dividing cells. Continuously proliferating cells are typical fordiseases like cancer and characterized by cells in all phases of thecell division cycle, namely in the G (“gap”) 1, S (“DNA synthesis”), G2and M (“mitosis”) phase.

Compounds according to aspect 1 of this invention more worthy to benoted are those compounds of formulae Ia or Ib as shown herein,

in which

-   Ra is —C(O)R1, in which    either-   R1 is 1-7C-alkyl, or imidazolo,    or-   R1 is 1-7C-alkyl which is substituted by one substituent selected    from R5,    or-   R1 is 2-4C-alkyl which is substituted by two hydroxyl groups on    different carbon atoms,    or-   R1 is 2,2-dimethyl-[1,3]dioxolan-4-yl, or 1-2C-alkyl which is    substituted by 2,2-dimethyl-[1,3]dioxolan-4-yl;    or in which-   Ra is —C(O)OR2, in which    either-   R2 is 1-7C-alkyl, 3-7C-cycloalkyl, phenyl, pyridyl,    (1-4C-alkoxycarbonyl)-phenyl, or (1-4C-alkoxy)-phenyl,    or-   R2 is 1-7C-alkyl which is substituted by one substituent selected    from R5,    or-   R2 is 3-4C-alkyl which is substituted by two hydroxyl groups on    different carbon atoms,    or-   R2 is 1-2C-alkyl which is substituted by    2,2-dimethyl-[1,3]dioxolan-4-yl;    or in which-   Ra is —C(O)SR2, in which    either-   R2 is 1-7C-alkyl,    or-   R2 is 1-7C-alkyl which is substituted by one substituent selected    from R5,    or-   R2 is 3-4C-alkyl which is substituted by two hydroxyl groups on    different carbon atoms,    or-   R2 is 1-2C-alkyl which is substituted by    2,2-dimethyl-[1,3]dioxolan-4-yl;    and in which    either-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl,    or-   Q is unsubstituted phenyl,    or-   Q is optionally substituted by Rca and/or Rcb, and is Har,    or-   Q is Cyc;-   in which-   each R5 is independently selected from the group consisting of:    -   1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy,        (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkoxy, hydroxyl,        1-4C-alkylcarbonyloxy, phenoxy, phenyl-1-4C-alkoxy,        1-4C-alkoxycarbonyl, carboxyl, amino, mono- or        di-1-4C-alkylamino, mono- or di-1-4C-alkylaminocarbonyl,        carbamoyl, ureido, guanidino, 1-4C-alkylcarbonylamino, Het, Har        and phenyl,    -   wherein each of said Har or phenyl radicals alone or part of        another group may be unsubstituted or optionally substituted by        one or two substituents independently selected from halogen,        1-4C-alkoxy, nitro, trifluoromethyl, 1-4C-alkyl,        1-4C-alkoxycarbonyl and carboxyl,-   Rba is halogen, 1-4C-alkyl, nitro, trifluoromethyl, 1-4C-alkoxy,    mono- or di-1-4C-alkylamino, hydroxyl, 1-4C-alkylcarbonyloxy, cyano,    phenyl, morpholino, phenoxy, hydroxy-2-4C-alkoxy,    1-4C-alkoxy-2-4C-alkoxy, 3-7C-cycloalkoxy,    3-7C-cycloalkyl-1-4C-alkoxy, phenyl-1-4C-alkoxy, cyano-1-4C-alkoxy,    or completely or predominantly fluorine-substituted 1-4C-alkoxy,-   Rbb is 1-4C-alkoxy, halogen, trifluoromethyl or 1-4C-alkyl,-   Rbc is 1-4C-alkoxy, halogen, trifluoromethyl or 1-4C-alkyl,-   Rca is halogen, 1-4C-alkyl, 1-4C-alkoxy, trifluoromethyl, phenyl,    phenoxy or morpholino,-   Rcb is halogen, 1-4C-alkyl or 1-4C-alkoxy,-   each Har is independently    either    -   a 5-membered monocyclic heteroaryl radical comprising one, two        or three heteroatoms independently selected from nitrogen,        oxygen and sulphur,    -   such as e.g. any one selected from furanyl, thiophenyl,        pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl,        imidazolyl, pyrazolyl, triazolyl, thiadiazolyl and oxadiazolyl,        or    -   a 6-membered monocyclic heteroaryl radical comprising one or two        nitrogen atoms, such as e.g. any one selected from pyridinyl,        pyrazinyl, pyridazinyl and pyrimidinyl,        or    -   a 9-membered fused bicyclic heteroaryl radical comprising one,        two or three heteroatoms independently selected from nitrogen,        oxygen and sulphur,    -   such as e.g. any one selected from indolyl, benzothiophenyl,        benzofuranyl, benzoxazoly, benzisoxazolyl, benzothiazolyl,        benzoisothiazolyl, benzimidazolyl, indazolyl, benzotriazolyl,        benzothiadiazolyl and benzoxadiazolyl,        or    -   a 10-membered fused bicyclic heteroaryl radical comprising one,        two or three heteroatoms independently selected from nitrogen,        oxygen and sulphur,    -   such as e.g. any one selected from quinolinyl, isoquinolinyl,        quinoxalinyl, quinazolinyl and cinnolinyl,-   whereby said Har radical is attached to the parent molecular group    via a ring carbon atom or ring nitrogen atom,-   Het is morpholino, piperidino, pyrrolidino, 4N—H-piperazino,    4N-(1-4C-alkyl)-piperazino, thiomorpholino, S-oxo-thiomorpholino or    S,S-dioxo-thiomorpholino,-   Cyc is optionally substituted by halogen on its benzene ring, and is    1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl,    2,2-difluoro-1,3-benzodioxolyl, 2,2-dimethyl-1,3-benzodioxolyl,    chromanyl, chromenyl or 2,3-dihydro-benzofuranyl,-   whereby said Cyc ring system is attached to the parent molecular    group via a substitutable benzoring carbon atom;    and the salts, solvates or the solvates of the salts thereof.

Compounds according to aspect 1 of this invention in particular worthyto be noted are those compounds of formula Ia as shown herein,

in which

-   Ra is —C(O)R1, in which    either-   R1 is 1-6C-alkyl,    or-   R1 is 1-4C-alkyl which is mono-substituted by R5, in which-   R5 is 1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy,    (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkoxy, hydroxyl, phenyl-1-4C-alkoxy,    phenoxy, pyridyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,    benzothiophenyl, thiazolyl, oxazolyl, 1N-(1-4C-alkyl)-imidazolyl,    1N-(1-4C-alkyl)-pyrazolyl, phenyl, 1-4C-alkoxycarbonyl, carboxyl,    amino, morpholino, piperidino, pyrrolidino,    4N-(1-4C-alkyl)-piperazino, mono- or di-1-4C-alkylamino, mono- or    di-1-4C-alkylaminocarbonyl, carbamoyl, ureido, guanidino, imidazolo,    triazolo, pyrazolo, 1-4C-alkylcarbonyloxy or    1-4C-alkylcarbonylamino,    -   wherein each of said pyridyl, pyrimidinyl, pyrazinyl, indolyl,        benzofuranyl, benzothiophenyl, thiazolyl, oxazolyl,        1N-(1-4C-alkyl)-imidazolyl, 1N-(1-4C-alkyl)-pyrazolyl,        imidazolo, pyrazolo or phenyl radicals alone or part of another        group may be unsubstituted or optionally substituted by one or        two substituents independently selected from halogen,        1-4C-alkoxy, nitro and 1-4C-alkyl,        or-   R1 is 3-4C-alkyl which is substituted by two hydroxyl groups on    different carbon atoms,    or-   R1 is 1-2C-alkyl which is substituted by    2,2-dimethyl-[1,3]dioxolan-4-yl;    or in which-   Ra is —C(O)OR2, in which    either-   R2 is 1-6C-alkyl,    or-   R2 is 3-7C-cycloalkyl, phenyl, pyridyl,    (1-4C-alkoxycarbonyl)-phenyl, or (1-4C-alkoxy)-phenyl,    or-   R2 is 1-4C-alkyl which is mono-substituted by R5, in which-   R5 is pyridyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,    benzothiophenyl, thiazolyl, oxazolyl, 1N-(1-4C-alkyl)-imidazolyl,    1N-(1-4C-alkyl)-pyrazolyl, phenyl, 1-4C-alkoxycarbonyl, carboxyl,    mono- or di-1-4C-alkylaminocarbonyl or carbamoyl,    -   wherein each of said pyridyl, pyrimidinyl, pyrazinyl, indolyl,        benzofuranyl, benzothiophenyl, thiazolyl, oxazolyl,        1N-(1-4C-alkyl)-imidazolyl, 1N-(1-4C-alkyl)-pyrazolyl or phenyl        radicals can be unsubstituted or optionally substituted by one        or two substituents independently selected from halogen,        1-4C-alkoxy, nitro and 1-4C-alkyl,        or-   R2 is 2-4C-alkyl which is mono-substituted by R5, in which-   R5 is 1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy,    (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkoxy, hydroxyl, phenyl-1-4C-alkoxy,    phenoxy, amino, morpholino, piperidino, pyrrolidino,    4N-(1-4C-alkyl)-piperazino, mono- or di-1-4C-alkylamino, ureido,    guanidino, imidazolo, triazolo, pyrazolo, 1-4C-alkylcarbonyloxy or    1-4C-alkylcarbonylamino,    -   wherein each of said imidazolo, pyrazolo or phenyl radicals        alone or part of another group can be unsubstituted or        optionally substituted by one or two substituents independently        selected from halogen, 1-4C-alkoxy, nitro and 1-4C-alkyl,        or-   R2 is 3-4C-alkyl which is substituted by two hydroxyl groups on    different carbon atoms,    or-   R2 is 1-2C-alkyl which is substituted by    2,2-dimethyl-[1,3]dioxolan-4-yl;    or in which-   Ra is —C(O)SR2, in which    either-   R2 is 1-6C-alkyl,    or-   R2 is 1-4C-alkyl which is mono-substituted by R5, in which-   R5 is pyridyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl,    benzothiophenyl, thiazolyl, oxazolyl, 1N-(1-4C-alkyl)-imidazolyl,    1N-(1-4C-alkyl)-pyrazolyl, phenyl, 1-4C-alkoxycarbonyl, carboxyl,    mono- or di-1-4C-alkylaminocarbonyl or carbamoyl,    -   wherein each of said pyridyl, pyrimidinyl, pyrazinyl, indolyl,        benzofuranyl, benzothiophenyl, thiazolyl, oxazolyl,        1N-(1-4C-alkyl)-imidazolyl, 1N-(1-4C-alkyl)-pyrazolyl or phenyl        radicals can be unsubstituted or optionally substituted by one        or two substituents independently selected from halogen,        1-4C-alkoxy, nitro and 1-4C-alkyl,        or-   R2 is 2-4C-alkyl which is mono-substituted by R5, in which-   R5 is 1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy,    (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkoxy, hydroxyl, phenyl-1-4C-alkoxy,    phenoxy, amino, morpholino, piperidino, pyrrolidino,    4N-(1-4C-alkyl)-piperazino, mono- or di-1-4C-alkylamino, ureido,    guanidino, imidazolo, triazolo, pyrazolo, 1-4C-alkylcarbonyloxy or    1-4C-alkylcarbonylamino,    -   wherein each of said imidazolo, pyrazolo or phenyl radicals        alone or part of another group can be unsubstituted or        optionally substituted by one or two substituents independently        selected from halogen, 1-4C-alkoxy, nitro and 1-4C-alkyl;        and in which        either-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl,    or-   Q is unsubstituted phenyl,    or-   Q is substituted by Rca and/or Rcb, and is thiophenyl, furanyl,    pyridyl, 1N-methyl-pyrrolyl, 1N-methyl-imidazolyl,    1N-methyl-pyrazolyl, benzothiophenyl or benzofuranyl,    or-   Q is unsubstituted, and is thiophenyl, furanyl, pyridyl,    1N—H-pyrrolyl, 1N—H-pyrazolyl, 1N—H-imidazolyl, 1N-methyl-pyrrolyl,    1N-methyl-imidazolyl, 1N-methyl-pyrazolyl, benzothiophenyl or    benzofuranyl,    or-   Q is 1,3-benzodioxol-5-yl, 1,3-benzodioxol-4-yl,    2,3-dihydro-1,4-benzodioxin-5-yl, 2,3-dihydro-1,4-benzodioxin-6-yl,    2,2-difluoro-1,3-benzodioxol-5-yl,    2,2-difluoro-1,3-benzodioxol-4-yl, 2,3-dihydro-benzofuran-4-yl,    2,3-dihydro-benzofuran-5-yl, 2,3-dihydro-benzofuran-6-yl or    2,3-dihydro-benzofuran-7-yl,    or-   Q is substituted by halogen on its benzene ring, and is    1,3-benzodioxol-5-yl, 1,3-benzodioxol-4-yl,    2,3-dihydro-1,4-benzodioxin-5-yl, 2,3-dihydro-1,4-benzodioxin-6-yl,    2,2-difluoro-1,3-benzodioxol-5-yl,    2,2-difluoro-1,3-benzodioxol-4-yl, 2,3-dihydro-benzofuran-4-yl,    2,3-dihydro-benzofuran-5-yl, 2,3-dihydro-benzofuran-6-yl or    2,3-dihydro-benzofuran-7-yl;    in which-   Rba is halogen, 1-4C-alkyl, nitro, trifluoromethyl, 1-4C-alkoxy,    mono- or di-1-4C-alkylamino, hydroxyl, 1-4C-alkylcarbonyloxy, cyano,    phenyl, morpholino, phenoxy, hydroxy-2-4C-alkoxy,    1-4C-alkoxy-2-4C-alkoxy, or completely or predominantly    fluorine-substituted 1-4C-alkoxy,-   Rbb is 1-4C-alkoxy, halogen or 1-4C-alkyl,-   Rbc is 1-4C-alkoxy or halogen,-   Rca is halogen, 1-4C-alkyl, 1-4C-alkoxy, phenyl, phenoxy or    morpholino,-   Rcb is halogen, 1-4C-alkyl or 1-4C-alkoxy,    and the salts, solvates or the solvates of the salts thereof.

Compounds according to aspect 1 of this invention in more particularworthy to be noted are those compounds of formula Ia as shown herein,

in which

-   Ra is —C(O)R1, in which    either-   R1 is 1-5C-alkyl,    or-   R1 is 1-4C-alkyl which is mono-substituted by R5, in which-   R5 is 1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy,    (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkoxy, hydroxyl, pyridyl,    pyrimidinyl, pyrazinyl, indolyl, thiazolyl, oxazolyl,    1N-(1-4C-alkyl)-imidazolyl, 1N-(1-4C-alkyl)-pyrazolyl, phenyl,    1-4C-alkoxycarbonyl, carboxyl, morpholino,    di-1-4C-alkylaminocarbonyl, carbamoyl, ureido, guanidino, imidazolo,    triazolo, pyrazolo or 1-4C-alkylcarbonyloxy,    or-   R1 is 3-4C-alkyl which is substituted by two hydroxyl groups on    different carbon atoms,    or-   R1 is 1-2C-alkyl which is substituted by    2,2-dimethyl-[1,3]dioxolan-4-yl;    or in which-   Ra is —C(O)OR2, in which    either-   R2 is 1-5C-alkyl,    or-   R2 is 3-6C-cycloalkyl, phenyl, pyridyl,    (1-4C-alkoxycarbonyl)-phenyl, or (1-4C-alkoxy)-phenyl,    or-   R2 is 1-4C-alkyl which is mono-substituted by R5, in which-   R5 is pyridyl, pyrimidinyl, pyrazinyl, 1N-(1-4C-alkyl)-imidazolyl,    1N-(1-4C-alkyl)-pyrazolyl, phenyl, (1-4C-alkoxy)-phenyl,    1-4C-alkoxycarbonyl, carboxyl, di-1-4C-alkylaminocarbonyl or    carbamoyl,    or-   R2 is 2-4C-alkyl which is mono-substituted by R5, in which-   R5 is 1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy,    (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkoxy, hydroxyl, phenyl-1-4C-alkoxy,    phenoxy, morpholino, piperidino, pyrrolidino,    4N-(1-4C-alkyl)-piperazino, di-1-4C-alkylamino, imidazolo, triazolo,    pyrazolo, 1-4C-alkylcarbonyloxy or 1-4C-alkylcarbonylamino,    or-   R2 is 3-4C-alkyl which is substituted by two hydroxyl groups on    different carbon atoms,    or-   R2 is 1-2C-alkyl which is substituted by    2,2-dimethyl-[1,3]dioxolan-4-yl;    or in which-   Ra is —C(O)SR2, in which    either-   R2 is 1-5C-alkyl,    or-   R2 is 2-4C-alkyl which is mono-substituted by R5, in which-   R5 is di-1-4C-alkylamino, hydroxyl or pyridyl;    and in which    either-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl,    or-   Q is unsubstituted phenyl,    or-   Q is substituted by Rca, and is thiophenyl, furanyl, pyridyl or    1N-(methyl)-pyrazolyl,    or-   Q is unsubstituted, and is thiophenyl, furanyl, pyridyl,    1N—(H)-pyrrolyl, 1N-(methyl)-pyrrolyl, benzothiophenyl or    benzofuranyl,    or-   Q is 1,3-benzodioxol-5-yl, 1,3-benzodioxol-4-yl,    2,3-dihydro-1,4-benzodioxin-5-yl, 2,3-dihydro-1,4-benzodioxin-6-yl,    2,2-difluoro-1,3-benzodioxol-5-yl,    2,2-difluoro-1,3-benzodioxol-4-yl, 2,3-dihydro-benzofuran-4-yl,    2,3-dihydro-benzofuran-5-yl, 2,3-dihydro-benzofuran-6-yl or    2,3-dihydro-benzofuran-7-yl,    or-   Q is substituted by halogen on its benzene ring, and is    1,3-benzodioxol-5-yl, 1,3-benzodioxol-4-yl,    2,3-dihydro-1,4-benzodioxin-5-yl, 2,3-dihydro-1,4-benzodioxin-6-yl,    2,2-difluoro-1,3-benzodioxol-5-yl,    2,2-difluoro-1,3-benzodioxol-4-yl, 2,3-dihydro-benzofuran-4-yl,    2,3-dihydro-benzofuran-5-yl, 2,3-dihydro-benzofuran-6-yl or    2,3-dihydro-benzofuran-7-yl;    in which-   Rba is halogen, 1-4C-alkyl, nitro, trifluoromethyl, 1-4C-alkoxy,    di-1-4C-alkylamino, hydroxyl, 1-4C-alkylcarbonyloxy, cyano, phenyl,    morpholino, phenoxy, hydroxy-2-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy,    or completely or predominantly fluorine-substituted 1-4C-alkoxy,-   Rbb is 1-4C-alkoxy, halogen or 1-4C-alkyl,-   Rbc is 1-4C-alkoxy or halogen,-   Rca is halogen, 1-4C-alkyl, 1-4C-alkoxy, phenyl, phenoxy or    morpholino,    and the salts, solvates or the solvates of the salts thereof.

Compounds according to aspect 1 of this invention to be emphasized arethose compounds of formula Ia as shown herein,

in which

-   Ra is —C(O)R1, in which    either-   R1 is methyl, ethyl, propyl or butyl,    or-   R1 is methyl which is mono-substituted by R5, ethyl which is    mono-substituted by R5, or propyl which is mono-substituted by R5,    in which-   R5 is methoxy, ethoxy, 2-methoxyethoxy, 2-(2-methoxyethoxy)-ethoxy,    hydroxyl, pyridyl, pyrimidinyl, pyrazinyl, indolyl, thiazolyl,    oxazolyl, 1N-methyl-imidazolyl, 1N-methyl-pyrazolyl, phenyl,    methoxycarbonyl, ethoxycarbonyl, carboxyl, dimethylaminocarbonyl,    morpholino, carbamoyl, ureido, guanidino, imidazolo, triazolo,    pyrazolo, ethylcarbonyloxy or methylcarbonyloxy,    or-   R1 is propyl or butyl, each of which is substituted by two hydroxyl    groups on different carbon atoms,    or-   R1 is methyl or ethyl, each of which is substituted by    2,2-dimethyl-[1,3]dioxolan-4-yl;    or in which-   Ra is —C(O)OR2, in which    either-   R2 is methyl, ethyl, propyl or butyl,    or-   R2 is cyclohexyl, phenyl, pyridyl, (1-2C-alkoxycarbonyl)-phenyl, or    (1-2C-alkoxy)-phenyl,    or-   R2 is methyl which is mono-substituted by R5, ethyl which is    mono-substituted by R5, or propyl which is mono-substituted by R5,    in which-   R5 is pyridyl, pyrimidinyl, pyrazinyl, 1N-methyl-imidazolyl,    1N-methyl-pyrazolyl, phenyl, (1-2C-alkoxy)-phenyl, methoxycarbonyl,    ethoxycarbonyl, carboxyl, di-methylaminocarbonyl or carbamoyl,    or-   R2 is ethyl which is mono-substituted by R5, or propyl which is    mono-substituted by R5, in which-   R5 is methoxy, ethoxy, 2-methoxyethoxy, 2-(2-methoxyethoxy)-ethoxy,    hydroxyl, benzyloxy, phenoxy, morpholino, piperidino, pyrrolidino,    4N-(methyl)-piperazino, dimethylamino, imidazolo, triazolo,    pyrazolo, methylcarbonyloxy, ethylcarbonyloxy, methylcarbonylamino    or ethylcarbonylamino,    or-   R2 is propyl or butyl, each of which is substituted by two hydroxyl    groups on different carbon atoms,    or-   R2 is methyl or ethyl, each of which is substituted by    2,2-dimethyl-[1,3]dioxolan-4-yl;    or in which-   Ra is —C(O)SR2, in which    either-   R2 is methyl, ethyl, propyl, butyl or pentyl,    or-   R2 is ethyl which is mono-substituted by R5, or propyl which is    mono-substituted by R5, in which-   R5 is dimethylamino, hydroxyl or pyridyl;    and in which    either-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl,    or-   Q is unsubstituted phenyl,    or-   Q is substituted by Rca, and is thiophenyl, furanyl, pyridyl or    1N-(methyl)-pyrazolyl,    or-   Q is unsubstituted, and is thiophenyl, furanyl, pyridyl,    1N—(H)-pyrrolyl, 1N-(methyl)-pyrrolyl, benzothiophenyl or    benzofuranyl,    or-   Q is 1,3-benzodioxol-5-yl, 1,3-benzodioxol-4-yl,    2,3-dihydro-1,4-benzodioxin-5-yl, 2,3-dihydro-1,4-benzodioxin-6-yl,    2,2-difluoro-1,3-benzodioxol-5-yl,    2,2-difluoro-1,3-benzodioxol-4-yl, 2,3-dihydro-benzofuran-4-yl,    2,3-dihydro-benzofuran-5-yl, 2,3-dihydro-benzofuran-6-yl or    2,3-dihydro-benzofuran-7-yl,    or-   Q is substituted by bromine, chlorine or fluorine on its benzene    ring, and is 1,3-benzodioxol-5-yl, 1,3-benzodioxol-4-yl,    2,3-dihydro-1,4-benzodioxin-5-yl, 2,3-dihydro-1,4-benzodioxin-6-yl,    2,2-difluoro-1,3-benzodioxol-5-yl,    2,2-difluoro-1,3-benzodioxol-4-yl, 2,3-dihydro-benzofuran-4-yl,    2,3-dihydro-benzofuran-5-yl, 2,3-dihydro-benzofuran-6-yl or    2,3-dihydro-benzofuran-7-yl;    in which-   Rba is chlorine, fluorine, bromine, methy, ethyl, methoxy, ethoxy,    isopropyloxy, propoxy, hydroxyl, nitro, trifluoromethyl,    dimethylamino, methylcarbonyloxy, cyano, phenyl, morpholino,    phenoxy, 2-hydroxyethoxy, difluoromethoxy or trifluoromethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine, bromine, ethyl or    methyl,-   Rbc is methoxy, ethoxy, fluorine or chlorine,-   Rca is chlorine, fluorine, bromine, methyl, ethyl, methoxy, ethoxy,    phenyl, phenoxy or morpholino,    and the salts, solvates or the solvates of the salts thereof.

Compounds according to aspect 1 of this invention to be more emphasizedare those compounds of formula Ia as shown herein,

in which

-   Ra is —C(O)R1, in which    either-   R1 is methyl, ethyl or propyl,    or-   R1 is methyl which is mono-substituted by R5, ethyl which is    mono-substituted by R5, or propyl which is mono-substituted by R5,    in which-   R5 is methoxy, 2-methoxyethoxy, hydroxyl, pyridyl, indolyl, phenyl,    methoxycarbonyl, ethoxycarbonyl, dimethylaminocarbonyl, guanidino,    imidazolo or methylcarbonyloxy;    or in which-   Ra is —C(O)OR2, in which    either-   R2 is methyl, ethyl, propyl or butyl,    or-   R2 is cyclohexyl, phenyl, pyridyl, (methoxycarbonyl)-phenyl, or    (methoxy)-phenyl,    or-   R2 is methyl which is mono-substituted by R5, ethyl which is    mono-substituted by R5, or propyl which is mono-substituted by R5,    in which-   R5 is pyridyl, phenyl, (methoxy)-phenyl, methoxycarbonyl or    ethoxycarbonyl,    or-   R2 is ethyl which is mono-substituted by R5, or propyl which is    mono-substituted by R5, in which-   R5 is methoxy, 2-methoxyethoxy, hydroxyl, benzyloxy, morpholino,    pyrrolidino, 4N-(methyl)-piperazino, dimethylamino, imidazolo or    methylcarbonylamino,    or-   R2 is 2,3-dihydroxypropyl,    or-   R2 is 2,2-dimethyl-[1,3]dioxolan-4-yl-methyl;    or in which-   Ra is —C(O)SR2, in which    either-   R2 is methyl, ethyl, propyl, butyl or pentyl,    or-   R2 is ethyl which is mono-substituted by R5, or propyl which is    mono-substituted by R5, in which-   R5 is dimethylamino;    and in which    either-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl,    or-   Q is unsubstituted phenyl,    or-   Q is substituted by Rca, and is thiophenyl, furanyl or    1N-(methyl)-pyrazolyl,    or-   Q is (morpholino)-pyridyl, or (phenoxy)-thiophenyl,    or-   Q is unsubstituted, and is thiophenyl, furanyl, pyridyl,    1N—(H)-pyrrolyl, benzothiophenyl, 1N-(methyl)-pyrrolyl or    benzofuranyl,    or-   Q is 1,3-benzodioxol-5-yl, 1,3-benzodioxol-4-yl,    2,2-difluoro-1,3-benzodioxol-5-yl, 2,2-difluoro-1,3-benzodioxol-4-yl    or 2,3-dihydro-benzofuran-4-yl,    or-   Q is substituted by bromine on its benzene ring, and is    1,3-benzodioxol-5-yl or 1,3-benzodioxol-4-yl;-   in which-   Rba is chlorine, fluorine, bromine, methy, ethyl, methoxy, ethoxy,    isopropyloxy, propoxy, hydroxyl, nitro, trifluoromethyl,    dimethylamino, methylcarbonyloxy, cyano, phenyl, morpholino,    phenoxy, difluoromethoxy or trifluoromethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine or methyl,-   Rbc is fluorine,-   Rca is chlorine, methyl, ethyl or phenyl,    and the salts, solvates or the solvates of the salts thereof.

Yet compounds according to aspect 1 of this invention to be moreemphasized are those compounds of formula Ia as shown herein,

in which

-   Ra is —C(O)R1, in which    either-   R1 is methyl, ethyl or propyl,    or-   R1 is methyl which is mono-substituted by R5, ethyl which is    mono-substituted by R5, or propyl which is mono-substituted by R5,    in which-   R5 is methoxy, ethoxy, 2-methoxyethoxy, 2-(2-methoxyethoxy)-ethoxy,    hydroxyl, pyridyl, pyrimidinyl, pyrazinyl, imidazolo, pyrazolo or    methylcarbonyloxy,    or-   R1 is 2,3-dihydroxy-propyl;    or in which-   Ra is —C(O)OR2, in which    either-   R2 is methyl, ethyl or propyl,    or-   R2 is methyl which is mono-substituted by R5, ethyl which is    mono-substituted by R5, or propyl which is mono-substituted by R5,    in which-   R5 is pyridyl, pyrazinyl or pyrimidinyl,    or-   R2 is ethyl which is mono-substituted by R5, or propyl which is    mono-substituted by R5, in which-   R5 is methoxy, ethoxy, 2-methoxyethoxy, 2-(2-methoxyethoxy)-ethoxy,    hydroxyl, imidazolo, pyrazolo or methylcarbonyloxy,    or-   R2 is 2,3-dihydroxy-propyl;    or in which-   Ra is —C(O)SR2, in which    either-   R2 is methyl, ethyl or propyl,    or-   R2 is methyl which is mono-substituted by R5, ethyl which is    mono-substituted by R5, or propyl which is mono-substituted by R5,    in which-   R5 is pyridyl or hydroxyl;    and in which    either-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl,    or-   Q is unsubstituted phenyl,    or-   Q is substituted by Rca, and is thiophenyl or furanyl,    or-   Q is unsubstituted, and is thiophenyl, furanyl or pyridyl,    or-   Q is 1,3-benzodioxol-5-yl, 1,3-benzodioxol-4-yl,    2,2-difluoro-1,3-benzodioxol-5-yl or    2,2-difluoro-1,3-benzodioxol-4-yl;    in which-   Rba is chlorine, fluorine, methy, ethyl, methoxy, ethoxy,    difluoromethoxy or trifluoromethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine or methyl,-   Rbc is fluorine,-   Rca is chlorine, methyl or ethyl,    and the salts, solvates or the solvates of the salts thereof.

Compounds according to aspect 1 of this invention to be in particularemphasized are those compounds of formula Ia as shown herein,

-   in which-   Ra is —C(O)R1, in which    either-   R1 is methyl, ethyl or propyl,    or-   R1 is (R5)-methyl, 2-(R5)-ethyl, or 3-(R5)-propyl, in which-   R5 is methoxy, ethoxy, 2-methoxyethoxy, hydroxyl, imidazolo,    pyridin-2-yl, pyridin-3-yl or pyridin-4-yl,    or-   R1 is 2,3-dihydroxy-propyl;    or in which-   Ra is —C(O)OR2, in which    either-   R2 is methyl, ethyl or propyl,    or-   R2 is (R5)-methyl, 2-(R5)-ethyl, or 3-(R5)-propyl, in which-   R5 is pyridin-2-yl, pyridin-3-yl or pyridin-4-yl,    or-   R2 is 2-(R5)-ethyl, or 3-(R5)-propyl, in which-   R5 is methoxy, ethoxy, 2-methoxyethoxy, imidazolo or hydroxyl,    or-   R2 is 2,3-dihydroxy-propyl;    or in which-   Ra is —C(O)SR2, in which    either-   R2 is methyl, ethyl or propyl,    or-   R2 is (R5)-methyl, 2-(R5)-ethyl, or 3-(R5)-propyl, in which-   R5 is pyridin-2-yl, pyridin-3-yl or pyridin-4-yl;    and in which    either-   Q is 2-methoxyphenyl, 2-chlorophenyl, 2-ethoxyphenyl or    2-methylphenyl,    or-   Q is 2-(Rba)-3-(Rbb)-phenyl, in which-   Rba is chlorine, methoxy, ethoxy or methyl,-   Rbb is methoxy, chlorine, fluorine or methyl,    or-   Q is 2-(Rba)-5-(Rbb)-phenyl, in which-   Rba is chlorine, methoxy, ethoxy or methyl,-   Rbb is methoxy, chlorine, fluorine or methyl,    or-   Q is unsubstituted phenyl,    or-   Q is unsubstituted, and is furan-2-yl, furan-3-yl or pyridin-3-yl,    or-   Q is 1,3-benzodioxol-4-yl or 2,2-difluoro-1,3-benzodioxol-4-yl;    and the salts, solvates or the solvates of the salts thereof.

Compounds according to aspect 1 of this invention to be in moreparticular emphasized are those compounds of formula Ia as shown herein,

in which

-   Ra is —C(O)R1, in which    either-   R1 is methyl, ethyl or propyl,    or-   R1 is methoxy-methyl, 2-methoxy-ethyl, (2-methoxyethoxy)-methyl,    2-(2-methoxyethoxy)-ethyl, hydroxy-methyl, 2-hydroxy-ethyl,    (pyridin-2-yl)-methyl, (pyridin-3-yl)-methyl, (pyridin-4-yl)-methyl,    2-(pyridin-2-yl)-ethyl, 2-(pyridin-3-yl)-ethyl, or    2-(pyridin-4-yl)-ethyl,    or-   R1 is 2,3-dihydroxy-propyl;    or in which-   Ra is —C(O)OR2, in which    either-   R2 is methyl, ethyl or propyl,    or-   R2 is 2-methoxy-ethyl, 2-(2-methoxyethoxy)-ethyl, 2-hydroxy-ethyl,    (pyridin-2-yl)-methyl, (pyridin-3-yl)-methyl, (pyridin-4-yl)-methyl,    2-(pyridin-2-yl)-ethyl, 2-(pyridin-3-yl)-ethyl, or    2-(pyridin-4-yl)-ethyl,    or-   R2 is 2,3-dihydroxy-propyl;    or in which-   Ra is —C(O)SR2, in which-   R2 is methyl, ethyl or propyl;    and in which    either-   Q is 2-methoxyphenyl,    or-   Q is 2-ethoxyphenyl,    or-   Q is 2-(Rba)-3-(Rbb)-phenyl, in which-   Rba is methoxy or ethoxy,-   Rbb is methoxy or methyl,    or-   Q is 2-(Rba)-5-(Rbb)-phenyl, in which-   Rba is methoxy or ethoxy,-   Rbb is methoxy or methyl,    or-   Q is unsubstituted phenyl,    or-   Q is unsubstituted, and is furan-2-yl, furan-3-yl or pyridin-3-yl,    or-   Q is 1,3-benzodioxol-4-yl;    and the salts, solvates or the solvates of the salts thereof.

Compounds according to aspect 1 of this invention to be in further moreparticular emphasized are those compounds of formula Ia as shown herein,

in which

-   Ra is —C(O)R1, in which    either-   R1 is methyl, ethyl or propyl,    or-   R1 is methoxy-methyl, 2-methoxy-ethyl, (2-methoxyethoxy)-methyl,    2-(2-methoxyethoxy)-ethyl, hydroxy-methyl, 2-hydroxy-ethyl,    (pyridin-2-yl)-methyl, (pyridin-3-yl)-methyl, (pyridin-4-yl)-methyl,    2-(pyridin-2-yl)-ethyl, 2-(pyridin-3-yl)-ethyl, or    2-(pyridin-4-yl)-ethyl,    or-   R1 is 2,3-dihydroxy-propyl;    or in which-   Ra is —C(O)OR2, in which    either-   R2 is methyl, ethyl or propyl,    or-   R2 is 2-methoxy-ethyl, 2-(2-methoxyethoxy)-ethyl, 2-hydroxy-ethyl,    (pyridin-2-yl)-methyl, (pyridin-3-yl)-methyl, (pyridin-4-yl)-methyl,    2-(pyridin-2-yl)-ethyl, 2-(pyridin-3-yl)-ethyl, or    2-(pyridin-4-yl)-ethyl,    or-   R2 is 2,3-dihydroxy-propyl;    or in which-   Ra is —C(O)SR2, in which-   R2 is methyl, ethyl or propyl;    and in which    either-   Q is 2-ethoxyphenyl,    or-   Q is 2-(Rba)-5-(Rbb)-phenyl, in which-   Rba is methoxy,-   Rbb is methoxy or methyl,    or-   Q is 2-(Rba)-5-(Rbb)-phenyl, in which-   Rba is ethoxy,-   Rbb is methoxy or methyl;    and the salts, solvates or the solvates of the salts thereof.

Compounds according to aspect 2 of this invention worthy to be noted arethose compounds of aspect 2,

wherein one or where possible more of the following restrictions apply:

-   a.) Ra is —C(O)R1, —C(O)OR2, —C(O)SR2, —C(O)N(R3)R4, or —S(O)₂R1;-   b.) Rb is as defined in formulae Ia or Ib as shown below;-   c.) Q is optionally substituted by Rba and/or Rbb and/or Rbc, and is    phenyl, or optionally substituted by Rca and/or Rcb, and is Har, or    Cyc;-   d.) R1, R2 and R3 may be the same or different and are independently    selected from the group consisting of: 1-7C-alkyl, Ar and Har,    wherein each of said 1-7C-alkyl, Ar and Har can be unsubstituted or    optionally substituted by at least one substituent independently    selected from R5;-   e.) R4 is hydrogen;-   f.) each R5, Rba, Rbb, Rbc, Rca and Rcb may be the same or different    and are independently selected from the group consisting of:    -   1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har, Het,    -   halogen, trifluoromethyl,    -   —C(O)R6, —C(O)OR7, —C(O)N(R8)R9,    -   —N(R10)C(O)R6, —N(R10)C(O)N(R8)R9,    -   —OR7 and —N(R8)R9, wherein each of said 1-7C-alkyl, Ar, Har and        Het can be unsubstituted or optionally substituted by at least        one substituent independently selected from R11;-   g.) R6, R7 and R8 may be the same or different and are independently    selected from the group consisting of: hydrogen and 1-7C-alkyl,    wherein said 1-7C-alkyl can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R12;-   h.) each R9 is independently selected from the group consisting of:    hydrogen and 1-7C-alkyl;-   i.) each R10 is hydrogen;-   j.) R11 is selected from the group consisting of: R5 as defined for    restriction f.);-   k.) R12 is selected from the group consisting of: R5 as defined for    restriction f.);-   l.) each Ar is phenyl;-   m.) each Har is independently any fully aromatic or partially    aromatic mono- or fused bicyclic ring or ring system made up of    -   a first constituent being a 5- or 6-membered monocyclic        unsaturated, aromatic heteroaryl ring A, which heteroaryl ring A        comprises one to four heteroatoms independently selected from        nitrogen, oxygen and sulfur,    -   and, optionally, fused to said first constituent,    -   a second constituent being a benzo group, any 3-7C-cycloalkane        group as defined herein, any additional heteroaryl ring A as        defined herein, or any heterocyclic ring B as defined herein,        whereby said Har ring or ring system is attached to the parent        molecular group via a substitutable ring carbon or ring nitrogen        atom;-   n.) each Het is independently any fully saturated or partially    unsaturated mono- or fused bicyclic ring or ring system made up of    -   a first constituent being a 3- to 7-membered monocyclic fully        saturated or partially unsaturated, non-aromatic heterocyclic        ring B,        -   which heterocyclic ring B comprises one to three heteroatoms            independently selected from nitrogen, oxygen and sulfur,        -   and which heterocyclic ring B is optionally substituted by            one or two oxo groups,    -   and, optionally, fused to said first constituent,    -   a second constituent being a benzo group, any 3-7C-cycloalkane        group as defined herein, or any additional heterocyclic ring B        as defined herein,    -   whereby said Het ring or ring system is attached to the parent        molecular group via a substitutable ring carbon or ring nitrogen        atom;-   o.) Cyc is as defined in aspect 2 above;-   p.) Q is attached to the adjacent 2-4C-alkenyl moiety via any one of    its substitutable ring carbon atoms.

Compounds according to aspect 2 of this invention further worthy to benoted are those compounds of formulae la or lb as shown below,

in which

-   Ra is —C(O)R1, —C(O)OR2, —C(O)SR2, —C(O)N(R3)R4, or —S(O)₂R1;    and    either-   Q is optionally substituted by Rba and/or Rbb and/or Rbc, and is    phenyl,    or-   Q is bonded to the adjacent unsaturated group via a ring carbon    atom, and is optionally substituted by Rca and/or Rcb, and is Har,    or-   Q is Cyc;    in which-   R1, R2 and R3 may be the same or different and are independently    selected from the group consisting of: 1-7C-alkyl, Ar and Har,    wherein each of said 1-7C-alkyl, Ar and Har can be unsubstituted or    optionally substituted by at (east one substituent independently    selected from R5;-   R4 is hydrogen;-   each R5, Rba, Rbb, Rbc, Rca and Rcb may be the same or different and    are independently selected from the group consisting of:    -   1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har, Het,    -   halogen, trifluoromethyl,    -   —C(O)R6, —C(O)OR7, —C(O)N(R8)R9,    -   —N(R10)C(O)R6, —N(R10)C(O)N(R8)R9,    -   —OR7 and —N(R8)R9, wherein each of said 1-7C-alkyl, Ar, Har and        Het can be unsubstituted or optionally substituted by at least        one substituent independently selected from R11;-   R6, R7 and R8 may be the same or different and are independently    selected from the group consisting of: hydrogen and 1-7C-alkyl,    wherein said 1-7C-alkyl can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R12;-   each R9 is independently selected from the group consisting of:    hydrogen and 1-7C-alkyl;-   each R10 is hydrogen;-   R11 is selected from the group consisting of: R5 as defined afore in    this paragraph;-   R12 is selected from the group consisting of: R5 as defined afore in    this paragraph;-   each Ar is phenyl;-   each Har is independently any fully aromatic or partially aromatic    mono- or fused bicyclic ring or ring system made up of-   a first constituent being a 5- or 6-membered monocyclic unsaturated,    aromatic heteroaryl ring A, which heteroaryl ring A comprises one to    four heteroatoms independently selected from nitrogen, oxygen and    sulfur,-   and, optionally, fused to said first constituent,-   a second constituent being a benzo group, or any additional    heteroaryl ring A as defined herein,    whereby said Har ring or ring system is attached to the parent    molecular group via a substitutable ring carbon or ring nitrogen    atom;-   each Het is independently any fully saturated or partially    unsaturated mono- or fused bicyclic ring or ring system made up of-   a first constituent being a 3- to 7-membered monocyclic fully    saturated or partially unsaturated, non-aromatic heterocyclic ring    B,    -   which heterocyclic ring B comprises one to three heteroatoms        independently selected from nitrogen, oxygen and sulfur,    -   and which heterocyclic ring B is optionally substituted by one        or two oxo groups,-   and, optionally, fused to said first constituent,-   a second constituent being a benzo group,    whereby said Het ring or ring system is attached to the parent    molecular group via a substitutable ring carbon or ring nitrogen    atom;-   Cyc is 1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl, or    2,3-dihydrobenzofuranyl;    and the salts, solvates or the solvates of the salts thereof.

In the compounds according to the present invention, the significancesmentioned in the following details/subdetails and/orvariants/subvariants can be considered individually or in anycombination thereof:

-   A first embodimental detail (detail a) of the compounds of aspect 1    or 2 according to this invention includes those compounds of    formulae I or, particularly, Ia or Ib as shown below,    in which-   Ra is —C(O)R1, —C(O)OR2, —C(O)SR2, —C(O)N(R3)R4, or —S(O)₂R1;    in which-   R1, R2 and R3 may be the same or different and are independently    selected from the group consisting of: 1-7C-alkyl, Ar and Har,    wherein each of said 1-7C-alkyl, Ar and Har can be unsubstituted or    optionally substituted by at least one substituent independently    selected from R5;-   R4 is hydrogen;-   each R5 is independently selected from the group consisting of:    -   1-7C-alkyl, Ar, Har, Het,    -   —C(O)R6, —C(O)OR7, —C(O)N(R8)R9,    -   N(R10)C(O)R6, —N(R10)C(O)N(R8)R9,    -   —OR7 and —N(R8)R9, wherein each of said 1-7C-alkyl, Ar, Har and        Het can be unsubstituted or optionally substituted by at least        one substituent independently selected from R11;-   R6, R7 and R8 may be the same or different and are independently    selected from the group consisting of: hydrogen and 1-7C-alkyl,    wherein said 1-7C-alkyl can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R12;-   each R9 is independently selected from the group consisting of:    hydrogen and 1-7C-alkyl;-   each R10 is hydrogen;-   R11 is selected from the group consisting of: R5 as defined in this    detail a;-   R12 is selected from the group consisting of: R5 as defined in this    detail a;-   each Ar is phenyl;-   each Har is independently any fully aromatic mono- or fused bicyclic    ring or ring system made up of a first constituent being a 5- or    6-membered monocyclic unsaturated, aromatic heteroaryl ring A,    -   which heteroaryl ring A comprises one to four heteroatoms        independently selected from nitrogen, oxygen and sulfur,-   and, optionally, fused to said first constituent,-   a second constituent being a benzo group,    whereby said Har ring or ring system is attached to the parent    molecular group via a substitutable ring carbon atom;-   each Het is independently any fully saturated or partially    unsaturated mono- or fused bicyclic ring or ring system made up of-   a first constituent being a 3- to 7-membered monocyclic fully    saturated or partially unsaturated, non-aromatic heterocyclic ring    B,    -   which heterocyclic ring B comprises one to three heteroatoms        independently selected from nitrogen, oxygen and sulfur,    -   and which heterocyclic ring B is optionally substituted by one        or two oxo groups,-   and, optionally, fused to said first constituent,-   a second constituent being a benzo group,    whereby said Het ring or ring system is attached to the parent    molecular group via a substitutable ring carbon or ring nitrogen    atom.

A second embodimental detail (detail b) of the compounds of aspect 1 or2 according to this invention includes those compounds of formulae I or,particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)R1, in which-   R1 is selected from the group consisting of:    -   hydrogen, 1-7C-alkyl, 3-7C-cycloalkyl, Ar and Har,    -   wherein 1-7C-alkyl is optionally substituted by at least one        substituent independently selected from R5 as defined in aspect        1 or 2, respectively, above, and    -   wherein each of said Ar and Har is optionally substituted by one        or two substituents independently selected from R5 as defined in        aspect 1 or 2, respectively, above.

Compounds according to detail b of this invention more worthy to bementioned in a subdetail thereof (detail b1a) include those compounds offormulae I or, particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)R1, in which-   R1 is hydrogen, 1-7C-alkyl, 3-7C-cycloalkyl, or 1-7C-alkyl    substituted by any one of R5 as defined in aspect 1 or 2 above.

Yet compounds according to detail b of this invention more worthy to bementioned in a subdetail thereof (detail b1b) include those compounds offormulae I or, particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)R1, in which-   R1 is phenyl, or phenyl substituted by any one of R5 as defined in    aspect 1 or 2 above.

Compounds according to detail b of this invention in particular worthyto be mentioned in a subdetail thereof (detail b2a) include thosecompounds of formulae I or, particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)R1, in which-   R1 is hydrogen, 1-7C-alkyl, 3-7C-cycloalkyl, or 1-7C-alkyl    substituted by R5, in which-   R5 is 3-7C-cycloalkyl, Ar, Har, Het,    -   —C(O)R6, —C(O)OR7, —C(O)N(R8)R9,    -   —N(R10)C(O)R6, —N(R10)C(O)OR7, —N(R10)C(O)N(R8)R9,        —N(R10)S(O)₂R6,    -   —N(R10)S(O)₂N(R8)R9,    -   —OR7, or —N(R8)R9, wherein each of said Ar, Har and Het can be        unsubstituted or optionally substituted by one to three        substituents independently selected from R11, in which-   R6, R7 and R8 may be the same or different and are independently    selected from the group consisting of: hydrogen, 1-7C-alkyl,    3-7C-cycloalkyl, Ar, Har and Het, wherein each of said 1-7C-alkyl,    3-7C-cycloalkyl, Ar, Har and Het can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R12,-   each R9 is independently selected from the group consisting of:    hydrogen, 1-7C-alkyl, or 3-7C-cycloalkyl, wherein each of said    1-7C-alkyl and 3-7C-cycloalkyl can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R12,-   each R10 is independently selected from the group consisting of:    hydrogen, 1-7C-alkyl, or 3-7C-cycloalkyl,-   R11 is as originally defined in aspect 1 or 2 above,-   each R12 is independently as originally defined in aspect 1 or 2    above,-   each Ar is phenyl,-   each Har is independently as originally defined in aspect 1 or 2    above,-   each Het is independently as originally defined in aspect 1 or 2    above.

Compounds according to detail b of this invention in more particularworthy to be mentioned in a subdetail thereof (detail b3a) include thosecompounds of formulae I or, particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)R1, in which-   R1 is hydrogen, 1-7C-alkyl, or 3-7C-cycloalkyl.

Yet compounds according to detail b of this invention in more particularworthy to be mentioned in a subdetail thereof (detail b3b) include thosecompounds of formulae I or, particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)R1, in which-   R1 is 1-7C-alkyl substituted by R5, in which-   R5 is Ar, Har, or Het, wherein each of said Ar, Har and Het can be    unsubstituted or optionally substituted by up to three substituents    independently selected from R11, in which-   R11 is as originally defined in aspect 1 or 2 above,-   Ar is phenyl,-   Har is as originally defined in aspect 1 or 2 above,-   Het is as originally defined in aspect 1 or 2 above.

Still yet compounds according to detail b of this invention in moreparticular worthy to be mentioned in a subdetail thereof (detail b3c)include those compounds of formulae I or, particularly, Ia or Ib asshown below,

in which

-   Ra is —C(O)R1, in which-   R1 is 1-7C-alkyl substituted by R5, in which-   R5 is —C(O)R6, —C(O)OR7, —C(O)N(R8)R9, —N(R10)C(O)R6,    —N(R10)C(O)OR7, —N(R10)C(O)N(R8)R9, —OR7 and —N(R8)R9, in which-   R6, R7 and R8 may be the same or different and are independently    selected from the group consisting of: hydrogen, 1-7C-alkyl and    3-7C-cycloalkyl, wherein said 1-7C-alkyl can be unsubstituted or    optionally substituted by any one of R12,-   each R9 is independently selected from the group consisting of:    hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl,-   each R10 is independently selected from the group consisting of:    hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl,-   each R12 is independently as originally defined in aspect 1 or 2    above.

Also still yet compounds according to detail b of this invention in moreparticular worthy to be mentioned in a subdetail thereof (detail b3d)include those compounds of formulae I or, particularly, Ia or Ib asshown below,

in which

-   Ra is —C(O)R1, in which-   R1 is phenyl, or phenyl substituted by R5, in which-   R5 is —OR7, in which-   R7 is selected from the group consisting of: hydrogen, 1-7C-alkyl,    3-7C-cycloalkyl, and Ar, wherein each of said 1-7C-alkyl,    3-7C-cycloalkyl and Ar can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R12,-   each R12 is independently as originally defined in aspect 1 or 2    above,-   each Ar is phenyl.

Further compounds according to detail b of this invention in moreparticular worthy to be mentioned in a subdetail thereof (detail b3e)include those compounds of formula I or, particularly, formula Ia asshown below,

in which

-   Ra is —C(O)R1, in which-   R1 is 1-4C-alkyl which is mono-substituted by R5, in which-   R5 is pyridyl, pyrimidinyl, pyrazinyl, indolyl, thiazolyl, oxazolyl,    1N-(1-4C-alkyl)-imidazolyl, 1N-(1-4C-alkyl)-pyrazolyl, morpholino,    imidazolo, triazolo or pyrazolo.

Yet further compounds according to detail b of this invention in moreparticular worthy to be mentioned in a subdetail thereof (detail b3f)include those compounds of formula I or, particularly, formula Ia asshown below,

in which

-   Ra is —C(O)R1, in which-   R1 is 1-4C-alkyl which is mono-substituted by R5, in which-   R5 is 1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy,    (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkoxy, hydroxyl,    1-4C-alkoxycarbonyl, carboxyl, di-1-4C-alkylaminocarbonyl,    carbamoyl, ureido, guanidino or 1-4C-alkylcarbonyloxy.

Compounds according to detail b of this invention in further moreparticular worthy to be mentioned in a subdetail thereof (detail b4a)include those compounds of formulae I or, particularly, Ia or Ib asshown below,

in which

-   Ra is —C(O)R1, in which-   R1 is 1-7C-alkyl.

Yet compounds according to detail b of this invention in further moreparticular worthy to be mentioned in a subdetail thereof (detail b4b)include those compounds of formulae I or, particularly, Ia or Ib asshown below,

in which

-   Ra is —C(O)R1, in which-   R1 is 1-7C-alkyl substituted by R5, in which-   R5 is phenyl, R51-substituted phenyl, Har, R52-substituted Har, Het,    or R53-substituted Het, in which-   R51 is 1-4C-alkoxy,-   Har is attached to the parent molecular group via a ring carbon or    ring nitrogen atom,    -   and is an unsaturated (aromatic) 5- or 6-membered monocyclic        ring comprising one to four heteroatoms independently selected        from nitrogen, oxygen and sulfur,    -   or an unsaturated (aromatic) 9- or 10-membered fused bicyclic        ring comprising one to four heteroatoms independently selected        from nitrogen, oxygen and sulfur,-   R52 is 1-4C-alkyl,-   Het is attached to the parent molecular group via a ring carbon or    ring nitrogen atom,    -   and is a saturated 3- to 7-membered monocyclic ring comprising        one to three heteroatoms independently selected from nitrogen,        oxygen and sulfur, and which is optionally substituted by one or        two oxo groups,    -   or a benzo fused derivative thereof,-   R53 is 1-4C-alkyl, or 1-4C-alkylcarbonyl.

Still yet compounds according to detail b of this invention in furthermore particular worthy to be mentioned in a subdetail thereof (detailb4c) include those compounds of formulae I or, particularly, Ia or Ib asshown below,

in which

-   Ra is —C(O)R1, in which-   R1 is 1-7C-alkyl substituted by R5, in which-   R5 is 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyl, carbamoyl, carboxyl,    mono- or di-1-4C-alkylaminocarbonyl, mono- or di-1-4C-alkylamino,    ureido, 1-4C-alkoxy, or phenyl-1-4C-alkoxy.

Also still yet compounds according to detail b of this invention infurther more particular worthy to be mentioned in a subdetail thereof(detail b4d) include those compounds of formulae I or, particularly, Iaor Ib as shown below,

in which

-   Ra is —C(O)R1, in which-   R1 is 1-7C-alkyl substituted by R5, in which-   R5 is phenyl.

Further still yet compounds according to detail b of this invention infurther more particular worthy to be mentioned in a subdetail thereof(detail b4e) include those compounds of formulae I or, particularly, Iaor Ib as shown below,

in which

-   Ra is —C(O)R1, in which-   R1 is phenyl, or phenyl substituted by R5, in which-   R5 is 1-4C-alkoxy.

Further compounds according to detail b of this invention in furthermore particular worthy to be mentioned in a subdetail thereof (detailb4f) include those compounds of formula I or, particularly, formula Iaas shown below,

in which

-   Ra is —C(O)R1, in which-   R1 is methyl, ethyl, propyl or butyl.

Yet further compounds according to detail b of this invention in furthermore particular worthy to be mentioned in a subdetail thereof (detailb4g) include those compounds of formula I or, particularly, formula Iaas shown below,

in which

-   Ra is —C(O)R1, in which-   R1 is (R5)-methyl, 2-(R5)-ethyl, or 3-(R5)-propyl, in which-   R5 is pyridyl, pyrimidinyl, pyrazinyl, imidazolo or pyrazolo.

Still yet further compounds according to detail b of this invention infurther more particular worthy to be mentioned in a subdetail thereof(detail b4h) include those compounds of formula I or, particularly,formula Ia as shown below,

in which

-   Ra is —C(O)R1, in which-   R1 is (R5)-methyl, 2-(R5)-ethyl, or 3-(R5)-propyl, in which-   R5 is methoxy, ethoxy, 2-methoxyethoxy, 2-(2-methoxyethoxy)ethoxy,    hydroxyl or methylcarbonyloxy.

Compounds according to detail b of this invention to be emphasized in asubdetail thereof (detail b5a) include those compounds of formula Ia asshown below,

in which

-   Ra is —C(O)R1, in which-   R1 is any one selected from methyl, ethyl and propyl.

Yet compounds according to detail b of this invention to be emphasizedin a subdetail thereof (detail b5b) include those compounds of formulaIa as shown below,

in which

-   Ra is —C(O)R1, in which-   R1 is any one selected from methoxy-methyl, 2-methoxy-ethyl,    (2-methoxyethoxy)-methyl, 2-(2-methoxyethoxy)-ethyl, hydroxy-methyl,    2-hydroxy-ethyl, (pyridin-2-yl)-methyl, (pyridin-3-yl)-methyl,    (pyridin-4-yl)-methyl, 2-(pyridin-2-yl)-ethyl,    2-(pyridin-3-yl)-ethyl and 2-(pyridin-4-yl)-ethyl.

Yet compounds according to detail b of this invention to be emphasizedin a subdetail thereof (detail b5c) include those compounds of formulaIa as shown below,

in which

-   Ra is —C(O)R1, in which-   R1 is 2,3-dihydroxypropyl.

A third embodimental detail (detail c) of the compounds of aspect 1 or 2according to this invention includes those compounds of formulae I or,particularly, Ia or Ib as shown below,

in which

-   Ra is —S(O)₂R1, in which-   R1 is Ar, Har, or Het, wherein each of said Ar and Har is optionally    substituted by one or two substituents independently selected from    R5 as defined in aspect 1 or 2, respectively, above.

A fourth embodimental detail (detail d) of the compounds of aspect 1 or2 according to this invention includes those compounds of formulae I or,particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is selected from the group consisting of:    -   1-7C-alkyl, 3-7C-cycloalkyl and Ar,    -   wherein 1-7C-alkyl is optionally substituted by at least one        substituent independently selected from R5 as defined in aspect        1 or 2, respectively, above, and    -   wherein Ar is optionally substituted by one or two substituents        independently selected from R5 as defined in aspect 1 or 2,        respectively, above.

Compounds according to detail d of this invention more worthy to bementioned in a subdetail thereof (detail d1a) include those compounds offormulae I or, particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is 1-7C-alkyl, 3-7C-cycloalkyl, or 1-7C-alkyl substituted by at    least one substituent independently selected from R5 as defined in    aspect 1 or 2 above.

Yet compounds according to detail d of this invention more worthy to bementioned in a subdetail thereof (detail d1b) include those compounds offormulae I or, particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is phenyl, or phenyl substituted by any one of R5 as defined in    aspect 1 or 2 above.

Compounds according to detail d of this invention in particular worthyto be mentioned in a subdetail thereof (detail d2) include thosecompounds of formulae I or, particularly, Ia or Ib as shown below, inwhich

-   Ra is —C(O)OR2, in which-   R2 is 1-7C-alkyl, 3-7C-cycloalkyl, or 1-7C-alkyl substituted by R5,    in which-   R5 is 3-7C-cycloalkyl, Ar, Har, Het,    -   —C(O)R6, —C(O)OR7, —C(O)N(R8)R9,    -   —N(R10)C(O)R6, —N(R10)C(O)OR7, —N(R10)C(O)N(R8)R9,        —N(R10)S(O)₂R6,    -   —N(R10)S(O)₂N(R8)R9,    -   —OR7 and —N(R8)R9, wherein each of said Ar, Har and Het can be        unsubstituted or optionally substituted by one to three        substituents independently selected from R11, in which-   R6, R7 and R8 may be the same or different and are independently    selected from the group consisting of: hydrogen, 1-7C-alkyl,    3-7C-cycloalkyl, Ar, Har and Het, wherein each of said 1-7C-alkyl,    3-7C-cycloalkyl, Ar, Har and Het can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R12,-   each R9 is independently selected from the group consisting of:    hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl, wherein each of said    1-7C-alkyl and 3-7C-cycloalkyl can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R12,-   each R10 is independently selected from the group consisting of:    hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl,-   R11 is as originally defined in aspect 1 or 2 above,-   each R12 is independently as originally defined in aspect 1 or 2    above,-   each Ar is phenyl,-   each Har is independently as originally defined in aspect 1 or 2    above,-   each Het is independently as originally defined in aspect 1 or 2    above.

Compounds according to detail d of this invention in more particularworthy to be mentioned in a subdetail thereof (detail d3a) include thosecompounds of formulae I or, particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is 1-7C-alkyl, or 3-7C-cycloalkyl.

Yet compounds according to detail d of this invention in more particularworthy to be mentioned in a subdetail thereof (detail d3b) include thosecompounds of formulae I or, particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is 1-7C-alkyl substituted by R5, in which-   R5 is Ar, Har, or Het, wherein each of said Ar, Har and Het can be    unsubstituted or optionally substituted by up to three substituents    independently selected from R11, in which-   R11 is as originally defined in aspect 1 or 2 above,-   Ar is phenyl,-   Har is as originally defined in aspect 1 or 2 above,-   Het is as originally defined in aspect 1 or 2 above.

Still yet compounds according to detail d of this invention in moreparticular worthy to be mentioned in a subdetail thereof (detail d3c)include those compounds of formulae I or, particularly, Ia or Ib asshown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is 2-7C-alkyl substituted by R5, in which-   R5 is —C(O)R6, —C(O)OR7, —C(O)N(R8)R9,

—N(R10)C(O)R6, —N(R10)C(O)OR7, —N(R10)C(O)N(R8)R9,

—OR7, or —N(R8)R(9), in which

-   R6, R7 and R8 may be the same or different and are independently    selected from the group consisting of: hydrogen, 1-7C-alkyl and    3-7C-cycloalkyl, wherein said 1-7C-alkyl can be unsubstituted or    optionally substituted by any of R12,-   each R9 is independently selected from the group consisting of:    hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl,-   each R10 is independently selected from the group consisting of:    hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl,-   each R12 is independently as originally defined in aspect 1 or 2    above.

Also still yet compounds according to detail d of this invention in moreparticular worthy to be mentioned in a subdetail thereof (detail d3d)include those compounds of formulae I or, particularly, Ia or Ib asshown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is phenyl, or phenyl substituted by R5, in which-   R5 is —OR7, in which-   R7 is selected from the group consisting of: hydrogen, 1-7C-alkyl,    3-7C-cycloalkyl, and Ar, wherein each of said 1-7C-alkyl,    3-7C-cycloalkyl and Ar can be unsubstituted or optionally    substituted by at least one substituent independently selected from    R12,    each R12 is independently as originally defined in aspect 1 or 2    above, each Ar is phenyl.

Further compounds according to detail d of this invention in moreparticular worthy to be mentioned in a subdetail thereof (detail d3e)include those compounds of formula I or, particularly, formula Ia asshown below,

in which

-   Ra is —C(O)OR2, in which    either-   R2 is 1-4C-alkyl which is mono-substituted by R5, in which-   R5 is pyridyl, pyrimidinyl, pyrazinyl, phenyl, or    (1-4C-alkoxy)-phenyl,    or-   R2 is 2-4C-alkyl which is mono-substituted by R5, in which-   R5 is morpholino, piperidino, pyrrolidino,    4N-(1-4C-alkyl)-piperazino, imidazolo, triazolo or pyrazolo.

Yet further compounds according to detail d of this invention in moreparticular worthy to be mentioned in a subdetail thereof (detail d3f)include those compounds of formula I or, particularly, formula Ia asshown below,

in which

-   Ra is —C(O)OR2, in which    either-   R2 is 1-4C-alkyl which is mono-substituted by R5, in which-   R5 is 1-4C-alkoxycarbonyl, carboxyl, di-1-4C-alkylaminocarbonyl or    carbamoyl,    or-   R2 is 2-4C-alkyl which is mono-substituted by R5, in which-   R5 is 1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy,    (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkoxy, hydroxyl, phenyl-1-4C-alkoxy,    phenoxy, di-1-4C-alkylamino, 1-4C-alkylcarbonyloxy or    1-4C-alkylcarbonylamino.

Compounds according to detail d of this invention in further moreparticular worthy to be mentioned in a subdetail thereof (detail d4a)include those compounds of formulae I or, particularly, Ia or Ib asshown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is 1-7C-alkyl.

Yet compounds according to detail d of this invention in further moreparticular worthy to be mentioned in a subdetail thereof (detail d4b)include those compounds of formulae I or, particularly, Ia or Ib asshown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is 1-7C-alkyl substituted by R5, in which-   R5 is phenyl, R51-substituted phenyl, Har, R52-substituted Har, Het,    or R53-substituted Het, in which-   R51 is 1-4C-alkoxy,-   Har is attached to the parent molecular group via a ring carbon or    ring nitrogen atom,    -   and is an unsaturated (aromatic) 5- or 6-membered monocyclic        ring comprising one to four heteroatoms independently selected        from nitrogen, oxygen and sulfur,    -   or an unsaturated (aromatic) 9- or 10-membered fused bicyclic        ring comprising one to four heteroatoms independently selected        from nitrogen, oxygen and sulfur,-   R52 is 1-4C-alkyl,-   Het is attached to the parent molecular group via a ring carbon or    ring nitrogen atom, and is a saturated 3- to 7-membered monocyclic    ring comprising one to three heteroatoms independently selected from    nitrogen, oxygen and sulfur, and which is optionally substituted by    one or two oxo groups,    -   or a benzo fused derivative thereof,-   R53 is 1-4C-alkyl, or 1-4C-alkylcarbonyl.

Still yet compounds according to detail d of this invention in furthermore particular worthy to be mentioned in a subdetail thereof (detaild4c) include those compounds of formulae I or, particularly, Ia or Ib asshown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is 2-7C-alkyl substituted by R5, in which-   R5 is 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyl, carbamoyl, carboxyl,    mono- or di-1-4C-alkylaminocarbonyl, mono- or di-1-4C-alkylamino,    ureido, 1-4C-alkoxy, or phenyl-1-4C-alkoxy.

Also still yet compounds according to detail d of this invention infurther more particular worthy to be mentioned in a subdetail thereof(detail d4d) include those compounds of formulae I or, particularly, Iaor Ib as shown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is 1-7C-alkyl substituted by R5, in which-   R5 is phenyl.

Further still yet compounds according to detail d of this invention infurther more particular worthy to be mentioned in a subdetail thereof(detail d4e) include those compounds of formulae I or, particularly, Iaor Ib as shown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is phenyl, or phenyl substituted by R5, in which-   R5 is 1-4C-alkoxy.

Further compounds according to detail d of this invention in furthermore particular worthy to be mentioned in a subdetail thereof (detaild4f) include those compounds of formula I or, particularly, formula Iaas shown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is methyl, ethyl, propyl or butyl.

Yet further compounds according to detail d of this invention in furthermore particular worthy to be mentioned in a subdetail thereof (detaild4g) include those compounds of formula I or, particularly, formula Iaas shown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is (R5)-methyl, 2-(R5)-ethyl, or 3-(R5)-propyl, in which-   R5 is pyridyl, pyrimidinyl or pyrazinyl.

Still yet further compounds according to detail d of this invention infurther more particular worthy to be mentioned in a subdetail thereof(detail d4h) include those compounds of formula I or, particularly,formula Ia as shown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is 2-(R5)-ethyl, or 3-(R5)-propyl, in which-   R5 is methoxy, ethoxy, 2-methoxyethoxy, 2-(2-methoxyethoxy)ethoxy,    hydroxyl or methylcarbonyloxy.

Compounds according to detail d of this invention to be emphasized in asubdetail thereof (detail d5a) include those compounds of formula Ia asshown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is any one selected from methyl, ethyl and propyl.

Yet compounds according to detail d of this invention to be emphasizedin a subdetail thereof (detail d5b) include those compounds of formulaIa as shown below,

in which

-   Ra is —C(O)OR2, in which-   R2 is any one selected from 2-methoxy-ethyl,    2-(2-methoxyethoxy)-ethyl, 2-hydroxy-ethyl, (pyridin-2-yl)-methyl,    (pyridin-3-yl)-methyl, (pyridin-4-yl)-methyl,    2-(pyridin-2-yl)-ethyl, 2-(pyridin-3-yl)-ethyl and    2-(pyridin-4-yl)-ethyl.

Yet compounds according to detail d of this invention to be emphasizedin a subdetail thereof (detail d5c) include those compounds of formulaIa as shown below,

in which

-   Ra is —C(O)OR2, in which-   R1 is 2,3-dihydroxypropyl.

A fifth embodimental detail (detail e) of the compounds of aspect 1 or 2according to this invention includes those compounds of formulae I or,particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)SR2, in which-   R2 is 1-7C-alkyl, 3-7C-cycloalkyl, or 1-7C-alkyl substituted by any    one of R5 as defined in aspect 1 or 2, respectively, above.

Compounds according to detail e of this invention in particular worthyto be mentioned in a subdetail thereof (detail e1) include thosecompounds of formulae I or, particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)SR2, in which-   R2 is 1-7C-alkyl.

Compounds according to detail e of this invention to be emphasized in asubdetail thereof (detail e2) include those compounds of formula Ia asshown below,

in which

-   Ra is —C(O)SR2, in which-   R2 is any one selected from methyl, ethyl and propyl.

Yet compounds according to detail e of this invention to be emphasizedin a subdetail thereof (detail e3) include those compounds of formula Iaas shown below,

in which

-   Ra is —C(O)SR2, in which-   R2 is any one selected from 2-methoxy-ethyl,    2-(2-methoxyethoxy)-ethyl, 2-hydroxy-ethyl, (pyridin-2-yl)-methyl,    (pyridin-3-yl)-methyl, (pyridin-4-yl)-methyl,    2-(pyridin-2-yl)-ethyl, 2-(pyridin-3-yl)-ethyl and    2-(pyridin-4-yl)-ethyl.

A sixth embodimental detail (detail f) of the compounds of aspect 1 or 2according to this invention includes those compounds of formulae I or,particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)N(R3)R4, in which-   R3 is selected from the group consisting of:    -   hydrogen, 1-7C-alkyl, or 3-7C-cycloalkyl,    -   wherein 1-7C-alkyl is optionally substituted by one substituent        selected from R5 as defined in aspect 1 or 2, respectively,        above;-   R4 is selected from the group consisting of:    -   hydrogen, 1-7C-alkyl, or 3-7C-cycloalkyl,    -   wherein 1-7C-alkyl is optionally substituted by one substituent        selected from R5 as defined in aspect 1 or 2, respectively,        above.

Compounds according to detail f of this invention more worthy to bementioned in a subdetail thereof (detail f1) include those compounds offormulae I or, particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)N(R3)R4, in which-   R3 is 1-7C-alkyl, 3-7C-cycloalkyl, or 1-7C-alkyl substituted by any    one of R5 as defined in aspect 1 or 2 above,-   R4 is hydrogen, 1-7C-alkyl, or 3-7C-cycloalkyl.

Compounds according to detail f of this invention in particular worthyto be mentioned in a subdetail thereof (detail f2) include thosecompounds of formulae I or, particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)N(R3)R4, in which-   R3 is 1-7C-alkyl, or 3-7C-cycloalkyl,-   R4 is hydrogen, 1-7C-alkyl, or 3-7C-cycloalkyl.

Yet compounds according to detail f of this invention in particularworthy to be mentioned in a subdetail thereof (detail f3) include thosecompounds of formulae I or, particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)N(R3)R4, in which-   R3 is 1-7C-alkyl substituted by any one of R5 as defined in aspect 2    above,-   R4 is hydrogen, 1-7C-alkyl, or 3-7C-cycloalkyl.

Compounds according to detail f of this invention in more particularworthy to be mentioned in a subdetail thereof (detail f4) include thosecompounds of formulae I or, particularly, Ia or Ib as shown below,

in which

-   Ra is —C(O)N(R3)R4, in which-   R3 is 1-7C-alkyl,-   R4 is hydrogen.

A seventh embodimental detail (detail g) of the compounds of aspect 1 or2 according to this invention includes those compounds of formulae I or,particularly, Ia or Ib as shown below,

in which

-   Ra is —S(O)₂N(R3)R4, in which-   R3 is selected from the group consisting of:    -   hydrogen, 1-7C-alkyl, or 3-7C-cycloalkyl,    -   wherein 1-7C-alkyl is optionally substituted by one substituent        selected from R5 as defined in aspect 1 or 2, respectively,        above;-   R4 is selected from the group consisting of:    -   hydrogen, 1-7C-alkyl, or 3-7C-cycloalkyl,    -   wherein 1-7C-alkyl is optionally substituted by one substituent        selected from R5 as defined in aspect 1 or 2, respectively,        above.

An interesting variant (variant a) of the compounds according to thisinvention includes those compounds of formula I wherein said compoundsare compounds from formula Ia:

Another variant (variant b) of the compounds according to this inventionincludes those compounds of formula I wherein said compounds arecompounds from formula Ib:

In the view of the foregoing variants and details, it is to be statedthat the variant concerning compounds of formula Ia is to be stressedwithin the meaning of this invention.

Another variant (variant c) of the compounds according to this inventionincludes those compounds of formula I, particularly of formula Ia or Ib,in which Q is optionally substituted by Rba and/or Rbb and/or Rbc, andis phenyl.

Another variant (variant d) of the compounds according to this inventionincludes those compounds of formula I, particularly of formula Ia or Ib,in which Q is optionally substituted by Rca and/or Rcb, and is Har.

Another variant (variant e) of the compounds according to this inventionincludes those compounds of formula I, particularly of formula Ia or Ib,in which Q is Cyc.

A more interesting variant (variant f) of the compounds according tothis invention includes those compounds of formula Ia, in which Q isoptionally substituted by Rba and/or Rbb and/or Rbc, and is phenyl.

Another more interesting variant (variant g) of the compounds accordingto this invention includes those compounds of formula Ia, in which Q isoptionally substituted by Rca and/or Rcb, and is Har.

Another more interesting variant (variant h) of the compounds accordingto this invention includes those compounds of formula Ia, in which Q isCyc.

Compounds according to variant h of this invention to be mentioned in asubvariant thereof (variant h1) include those compounds of formula Ia,in which

-   Q is Cyc, in which-   Cyc is 1,3-benzodioxolyl, or 2,3-dihydro-1,4-benzodioxinyl.

Compounds according to variant h of this invention to be mentioned in asubvariant thereof (variant h2) include those compounds of formula Ia,in which

-   Q is Cyc, in which-   Q is 1,3-benzodioxol-5-yl, 1,3-benzodioxol-4-yl,    2,3-dihydro-1,4-benzodioxin-5-yl, 2,3-dihydro-1,4-benzodioxin-6-yl,    2,2-difluoro-1,3-benzodioxol-5-yl,    2,2-difluoro-1,3-benzodioxol-4-yl, 2,3-dihydro-benzofuran-4-yl,    2,3-dihydro-benzofuran-5-yl, 2,3-dihydro-benzofuran-6-yl,    2,3-dihydro-benzofuran-7-yl, or 4-bromo-1,3-benzodioxol-5-yl.

Compounds according to variant h of this invention to be mentioned in asubvariant thereof (variant h3) include those compounds of formula Ia,in which

-   Q is Cyc, in which-   Q is 1,3-benzodioxol-5-yl, 1,3-benzodioxol-4-yl,    2,2-difluoro-1,3-benzodioxol-5-yl,    2,2-difluoro-1,3-benzodioxol-4-yl, or 4-bromo-1,3-benzodioxol-5-yl.

Compounds according to variant h of this invention to be mentioned in asubvariant thereof (variant h4) include those compounds of formula Ia,in which

-   Q is Cyc, in which-   Q is 1,3-benzodioxol-4-yl.

Another more interesting variant (variant i) of the compounds accordingto this invention includes those compounds of formula Ia, in which Q isRba- and/or Rbb- and/or Rbc-substituted phenyl.

Compounds according to variant i of this invention to be mentioned in asubvariant thereof (variant i1) include those compounds of formula Ia,in which

-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in which-   Rba, Rbb and Rbc have the meanings as given in any of the aspects 1    or 2.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i2) include those compounds offormula Ia, in which

-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in which-   Rba is 1-4C-alkyl, halogen, trifluoromethyl, 1-4C-alkoxy, nitro,    hydroxyl, amino, or mono- or di-1-4C-alkylamino,-   Rbb is halogen, or 1-4C-alkoxy,-   Rbc is 1-4C-alkoxy.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i3) include those compounds offormula Ia, in which

-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in which-   Rba is 1-4C-alkyl, halogen, trifluoromethyl, 1-4C-alkoxy, nitro, or    di-1-4C-alkylamino,-   Rbb is halogen, or 1-4C-alkoxy,-   Rbc is 1-4C-alkoxy.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i4) include those compounds offormula Ia, in which

-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in which-   Rba is halogen, 1-4C-alkyl, nitro, trifluoromethyl, 1-4C-alkoxy,    di-1-4C-alkylamino, hydroxyl, 1-4C-alkylcarbonyloxy, cyano, phenyl,    morpholino, phenoxy, hydroxy-2-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy,    or completely or predominantly fluorine-substituted 1-4C-alkoxy,-   Rbb is 1-4C-alkoxy, halogen or 1-4C-alkyl,-   Rbc is 1-4C-alkoxy or halogen.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i5) include those compounds offormula Ia, in which

-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in which-   Rba is chlorine, fluorine, bromine, methyl, ethyl, methoxy, ethoxy,    isopropyloxy, propoxy, hydroxyl, nitro, trifluoromethyl,    dimethylamino, methylcarbonyloxy, cyano, phenyl, morpholino,    phenoxy, difluoromethoxy or trifluoromethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine or methyl,-   Rbc is fluorine or chlorine.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i6) include those compounds offormula Ia, in which

-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in which-   Rba is chlorine, fluorine, bromine, methyl, ethyl, methoxy, ethoxy,    difluoromethoxy or trifluoromethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine or methyl,-   Rbc is fluorine.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i7) include those compounds offormula Ia, in which

-   Q is 2-(Rba)-phenyl which is optionally substituted by Rbb and/or    Rbc.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i8) include those compounds offormula Ia, in which

-   Q is phenyl which is substituted by Rba and Rbb.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i9) include those compounds offormula Ia, in which

-   Q is Rbb-substituted 2-(Rba)-phenyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i10) include those compounds offormula Ia, in which

-   Q is 2-(Rba)-5-(Rbb)-phenyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i11) include those compounds offormula Ia, in which

-   Q is 2-(Rba)-3-(Rbb)-phenyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i12) include those compounds offormula Ia, in which

-   Q is 5-(Rba)-2-(Rbb)-phenyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i13) include those compounds offormula Ia, in which

-   Q is 3-(Rba)-2-(Rbb)-phenyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i14) include those compounds offormula Ia, in which

-   Q is phenyl which is mono-substituted by Rba.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i15) include those compounds offormula Ia, in which

-   Q is phenyl which is mono-substituted by Rba, in which-   Rba is substituted in the para, or, in particular, meta, or, in more    particular, ortho position with respect to the binding position in    which the phenyl ring is attached to the ethenyl moiety.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i16) include those compounds offormula Ia, in which

-   Q is phenyl which is mono-substituted by Rba on the ortho position    with respect to the binding position in which the phenyl ring is    attached to the ethenyl moiety, i.e. 2-(Rba)-phenyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i17) include those compounds offormula Ia, in which

-   Q is phenyl which is mono-substituted by Rba on the meta position    with respect to the binding position in which the phenyl ring is    attached to the ethenyl moiety, i.e. 3-(Rba)-phenyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i18) include those compounds offormula Ia, in which

-   Q is 2-(Rba)-phenyl which optionally substituted by Rbb and/or Rbc,    in which-   Rba is chlorine, fluorine, methyl, ethyl, methoxy, ethoxy,    difluoromethoxy or trifluoromethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine or methyl,-   Rbc is fluorine.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i19) include those compounds offormula Ia, in which

-   Q is 2-(Rba)-phenyl which optionally substituted by Rbb and/or Rbc,    in which-   Rba is chlorine, methoxy or, particularly, ethoxy.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i20) include those compounds offormula Ia, in which

-   Q is 2-(Rba)-5-(Rbb)-phenyl, in which-   Rba is chlorine, fluorine, methyl, ethyl, methoxy, ethoxy,    difluoromethoxy or trifluoromethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine or methyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i21) include those compounds offormula Ia, in which

-   Q is 2-(Rba)-3-(Rbb)-phenyl, in which-   Rba is chlorine, fluorine, methyl, ethyl, methoxy, ethoxy,    difluoromethoxy or trifluoromethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine or methyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i22) include those compounds offormula Ia, in which

-   Q is phenyl which is mono-substituted by Rba, in which-   Rba is chlorine, fluorine, bromine, methyl, ethyl, methoxy, ethoxy,    isopropyloxy, propoxy, hydroxyl, nitro, trifluoromethyl,    dimethylamino, methylcarbonyloxy, cyano, phenyl, morpholino,    phenoxy, difluoromethoxy, trifluoromethoxy or 2-hydroxyethoxy.

Compounds according to variant f of this invention to be mentioned inanother subvariant thereof (variant i23) include those compounds offormula Ia, in which

-   Q is phenyl which is mono-substituted by Rba, in which-   Rba is chlorine, methyl, ethyl, methoxy or ethoxy.

Compounds according to variant f of this invention to be mentioned inanother subvariant thereof (variant i24) include those compounds offormula Ia, in which

-   Q is 2-(Rba)-phenyl, in which-   Rba is chlorine, fluorine, bromine, methyl, ethyl, methoxy, ethoxy,    isopropyloxy, propoxy, hydroxyl, nitro, trifluoromethyl,    dimethylamino, methylcarbonyloxy, cyano, phenyl, morpholino,    phenoxy, difluoromethoxy, trifluoromethoxy or 2-hydroxyethoxy.

Compounds according to variant f of this invention to be mentioned inanother subvariant thereof (variant i25) include those compounds offormula Ia, in which

-   Q is 2-(Rba)-phenyl, in which-   Rba is chlorine, methyl, ethyl, methoxy or ethoxy.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i26) include those compounds offormula Ia, in which

-   Q is phenyl which is substituted by Rba and Rbb, in which-   Rba is chlorine, methyl, ethyl, methoxy or ethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine or methyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i27) include those compounds offormula Ia, in which

-   Q is Rbb-substituted 2-(Rba)-phenyl, in which-   Rba is chlorine, methyl, ethyl, methoxy or ethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine or methyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i28) include those compounds offormula Ia, in which

-   Q is Rbb-substituted 2-(Rba)-phenyl, in which-   Rba is methoxy or ethoxy,-   Rbb is methoxy, fluorine, chlorine or methyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i29) include those compounds offormula Ia, in which

-   Q is Rbb-substituted 2-(Rba)-phenyl, in which-   Rba is methyl, ethyl or chlorine,-   Rbb is methoxy, fluorine, chlorine or methyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i30) include those compounds offormula Ia, in which

-   Q is 2-(Rba)-3-(Rbb)-phenyl, in which    either-   Rba is ethoxy, and-   Rbb is methoxy, fluorine, chlorine or methyl.    or-   Rba is methoxy, and-   Rbb is methoxy, fluorine, chlorine or methyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i31) include those compounds offormula Ia, in which

-   Q is 2-(Rba)-5-(Rbb)-phenyl, in which    either-   Rba is ethoxy, and-   Rbb is methoxy, fluorine, chlorine or methyl.    or-   Rba is methoxy, and-   Rbb is methoxy, fluorine, chlorine or methyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i32) include those compounds offormula Ia, in which

-   Q is any one selected from 2-methoxyphenyl, 3-methoxyphenyl,    4-methoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl,    2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-methylphenyl,    3-methylphenyl, 4-methylphenyl, 2-fluorophenyl, 3-fluorophenyl,    4-fluorophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl,    2-trifluoromethylphenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,    4-hydroxyphenyl,-   2-acetoxyphenyl, 2-bromophenyl, 2-ethylphenyl, 2-cyanophenyl,    2-morpholinophenyl, 2-phenylphenyl, 2-isopropoxyphenyl,    2-propoxyphenyl, 2-phenoxyphenyl, 2-(2-hydroxyethyl)-phenyl,    2-difluoromethoxyphenyl and 2-trifluoromethoxyphenyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i33) include those compounds offormula Ia, in which

-   Q is 2-methoxyphenyl or 2-ethoxyphenyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i34) include those compounds offormula Ia, in which

-   Q is any one selected from 2,3-difluorophenyl,    2-fluoro-3-chlorophenyl, 2-fluoro-4-chlorophenyl,    2-chloro-6-fluorophenyl, 2,6-dichlorophenyl, 2,4-dichlorophenyl,    2,6-difluorophenyl, 2-fluoro-4-methoxyphenyl,    2-methyl-5-fluorophenyl, 2-methyl-3-fluorophenyl,    2-methyl-4-fluorophenyl, 2,3-dimethylphenyl, 2,3-dimethoxyphenyl,    2-ethoxy-3-methoxyphenyl, 2,5-dimethoxyphenyl and    2,6-dimethoxyphenyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i35) include those compounds offormula Ia, in which

-   Q is any one selected from 2,3-dimethoxyphenyl,    2-ethoxy-3-methoxyphenyl, 2-ethoxy-5-methoxyphenyl and    2,5-dimethoxyphenyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i36) include those compounds offormula Ia, in which

-   Q is any one selected from 2-methoxy-5-chlorophenyl,    2-methoxy-5-methylphenyl, 2-ethoxy-5-chlorophenyl,    2-ethoxy-5-methylphenyl, 2-chloro-5-methoxyphenyl and    2,5-dimethoxyphenyl.

Compounds according to variant i of this invention to be mentioned inanother subvariant thereof (variant i37) include those compounds offormula Ia, in which

-   Q is any one selected from 2-methoxy-3-chlorophenyl,    2-methoxy-3-methylphenyl, 2-ethoxy-3-chlorophenyl,    2-ethoxy-3-methylphenyl, 2-chloro-3-methoxyphenyl and    2,3-dimethoxyphenyl.

Another more interesting variant (variant j) of the compounds accordingto this invention includes those compounds of formula Ia, in which Q isunsubstituted phenyl.

Another more interesting variant (variant k) of the compounds accordingto this invention includes those compounds of formula Ia, in which Q isRca- and/or Rcb-substituted Har.

Compounds according to variant k of this invention to be mentioned in asubvariant thereof (variant k1) include those compounds of formula Ia,in which

-   Q is Rca- and/or Rcb-substituted Har, in which-   Har is pyridyl, furanyl, thiophenyl, or indolyl,-   Rca is 1-4C-alkyl, or halogen,-   Rcb is halogen.

Compounds according to variant k of this invention to be mentioned inanother subvariant thereof (variant k2) include those compounds offormula Ia, in which

-   Q is Rca-substituted Har, in which-   Har is pyridyl, furanyl, thiophenyl or 1N-(methyl)-pyrazolyl,-   Rca is chlorine, fluorine, bromine, methyl, ethyl, methoxy, ethoxy,    phenyl, phenoxy or morpholino.

Compounds according to variant k of this invention to be mentioned inanother subvariant thereof (variant k3) include those compounds offormula Ia, in which

-   Q is (morpholino)-pyridyl, (phenoxy)-thiophenyl, or Rca-substituted    Har, in which-   Har is furanyl, thiophenyl or 1N-(methyl)-pyrazolyl,-   Rca is chlorine, methyl, ethyl or phenyl.

Compounds according to variant k of this invention to be mentioned inanother subvariant thereof (variant k4) include those compounds offormula Ia, in which

-   Q is any one selected from (chloro)-thiophenyl, such as e.g.    3-chloro-thiophen-2-yl or 5-chloro-thiophen-2-yl; (chloro)-furanyl,    such as e.g. 5-chloro-furan-2-yl; (methyl)-furanyl, such as e.g.    5-methyl-furan-2-yl; (ethyl)-furanyl, such as e.g.    5-ethyl-furan-2-yl; (methyl)-thiophenyl, such as e.g.    3-methyl-thiophen-2-yl or 5-methyl-thiophen-2-yl;    (phenoxy)-thiophenyl, such as e.g. 3-phenoxy-thiophen-2-yl;    (phenyl)-thiophenyl, such as e.g. 5-phenyl-thiophen-2-yl;    (phenyl)-furanyl, such as e.g. 5-phenyl-furan-2-yl;    (chloro)-1N-(methyl)-pyrazolyl, such as e.g.    4-chloro-1N-(methyl)-pyrazol-3-yl; or (morpholino)-pyridyl, such as    e.g. 2-morpholino-pyridin-3-yl.

Another more interesting variant (variant I) of the compounds accordingto this invention includes those compounds of formula Ia, in which Q isunsubstituted Har.

Compounds according to variant I of this invention to be mentioned in asubvariant thereof (variant I1) include those compounds of formula Ia,in which

-   Q is unsubstituted Har, in which-   Har is pyridyl, thiophenyl or furanyl.

Compounds according to variant I of this invention to be mentioned in aanother subvariant thereof (variant I2) include those compounds offormula Ia, in which

-   Q is unsubstituted Har, in which-   Har is pyridyl, thiophenyl, furanyl, benzothiophenyl, benzofuranyl,    1N—(H)-pyrrolyl or 1N-(methyl)-pyrrolyl.

Compounds according to variant I of this invention to be mentioned inanother subvariant thereof (variant I3) include those compounds offormula Ia, in which

-   Q is any one selected from pyridin-2-yl, pyridin-3-yl, pyridin-4-yl,    thiophen-2-yl, thiophen-3-yl, furan-2-yl, furan-3-yl,    1N—(H)-pyrrol-2-yl, 1N—(H)-pyrrol-3-yl, 1N-(methyl)-pyrrol-2-yl and    1N-(methyl)-pyrrol-3-yl.

Compounds according to variant I of this invention to be mentioned inanother subvariant thereof (variant I3) include those compounds offormula Ia, in which

-   Q is any one selected from pyridin-3-yl, thiophen-2-yl,    thiophen-3-yl, furan-2-yl and furan-3-yl.

Compounds according to aspect 2 of this invention more worthy to benoted are those compounds of formulae Ia or Ib,

in which, in a first alternative,

-   Ra is —C(O)R1, in which,-   R1 is 1-7C-alkyl, or 1-7C-alkyl substituted by R5, in which    either-   R5 is 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyl, carbamoyl, guanidino,    amidino, carboxyl, mono- or di-1-4C-alkylaminocarbonyl, mono- or    di-1-4C-alkylamino, ureido, 1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, or    phenyl-1-4C-alkoxy,    or-   R5 is phenyl, R51-substituted phenyl, Har, R52-substituted Har, Het,    or R53-substituted Het, in which-   R51 is 1-4C-alkoxy,-   Har is attached to the parent molecular group via a ring carbon or    ring nitrogen atom,    -   and is an unsaturated (aromatic) 5-membered ring comprising one        to four heteroatoms independently selected from nitrogen, oxygen        and sulfur,    -   or an unsaturated (aromatic) 6-membered ring comprising one or        two nitrogen atoms,    -   or an unsaturated (aromatic) 9-membered fused bicyclic ring        system made up of a benzene ring fused to an unsaturated        (aromatic) 5-membered ring comprising one to three heteroatoms    -   independently selected from nitrogen, oxygen and sulfur,    -   or an unsaturated (aromatic) 10-membered fused bicyclic ring        system made up of a benzene ring fused to an unsaturated        (aromatic) 6-membered ring comprising one or two nitrogen atoms,-   R52 is 1-4C-alkyl,-   Het is attached to the parent molecular group via a ring nitrogen    atom,    -   and is a saturated 3- to 7-membered monocyclic ring comprising        one or two heteroatoms independently selected from nitrogen,        oxygen and sulfur, and which is optionally substituted by one or        two oxo groups,    -   or a benzo-fused derivative thereof,-   R53 is 1-4C-alkyl, or 1-4C-alkylcarbonyl;    or in which, in a second alternative,-   Ra is —C(O)OR2, in which,-   R2 is 1-7C-alkyl,    or-   R2 is 2-7C-alkyl substituted by R5, in which either-   R5 is 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyl, guanidino, amidino,    carbamoyl, carboxyl, mono- or di-1-4C-alkylaminocarbonyl, mono- or    di-1-4C-alkylamino, ureido, 1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, or    phenyl-1-4C-alkoxy,    or-   R5 is Het, or R53-substituted Het, in which-   Het is attached to the parent molecular group via a ring nitrogen    atom,    -   and is a saturated 3- to 7-membered monocyclic ring comprising        one or two heteroatoms independently selected from nitrogen,        oxygen and sulfur, and which is optionally substituted by one or        two oxo groups,    -   or a benzo-fused derivative thereof,-   R53 is 1-4C-alkyl, or 1-4C-alkylcarbonyl,    or-   R2 is 1-7C-alkyl substituted by R5, in which-   R5 is phenyl, R51-substituted phenyl, Har, or R52-substituted Har,    in which-   R51 is 1-4C-alkoxy,-   Har is attached to the parent molecular group via a ring carbon or    ring nitrogen atom,    -   and is an unsaturated (aromatic) 5-membered ring comprising one        to four heteroatoms independently selected from nitrogen, oxygen        and sulfur,    -   or an unsaturated (aromatic) 6-membered ring comprising one or        two nitrogen atoms,    -   or an unsaturated (aromatic) 9-membered fused bicyclic ring        system made up of a benzene ring fused to an unsaturated        (aromatic) 5-membered ring comprising one to three heteroatoms        independently selected from nitrogen, oxygen and sulfur,    -   or an unsaturated (aromatic) 10-membered fused bicyclic ring        system made up of a benzene ring fused to an unsaturated        (aromatic) 6-membered ring comprising one or two nitrogen atoms,-   R52 is 1-4C-alkyl;    or in which, in a third alternative,-   Ra is —C(O)SR2, in which,-   R2 is 1-7C-alkyl;    and in which    either-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in which-   Rba, Rbb and Rbc are independently as originally defined in aspect 2    above,    or, particularly,-   Q is unsubstituted phenyl,    or, yet particularly,-   Q is 2-chloro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl,    2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl,    2-trifluoromethyl-phenyl, 2-nitro-phenyl, 3-nitro-phenyl,    4-nitro-phenyl, 2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl,    2-methoxy-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl,    2,3-dimethoxy-phenyl, or 2,4-dichloro-phenyl,    or, still yet particularly,-   Q is thiophenyl, furanyl or pyridyl;    and the salts, solvates or the solvates of the salts thereof.

Yet compounds according to aspect 2 of this invention more worthy to benoted are those compounds of formulae Ia or Ib,

in which

-   Ra is —C(O)N(R3)R4, in which,-   R3 is 1-7C-alkyl,    or-   R3 is 2-7C-alkyl substituted by R5, in which either-   R5 is 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyl, carbamoyl, carboxyl,    mono- or di-1-4C-alkylaminocarbonyl, mono- or di-1-4C-alkylamino,    ureido, 1-4C-alkoxy, or phenyl-1-4C-alkoxy,    or-   R5 is Het, or R53-substituted Het, in which-   Het is attached to the parent molecular group via a ring nitrogen    atom,    -   and is a saturated 3- to 7-membered monocyclic ring comprising        one or two heteroatoms independently selected from nitrogen,        oxygen and sulfur, and which is optionally substituted by one or        two oxo groups,    -   or a benzo-fused derivative thereof,-   R53 is 1-4C-alkyl, or 1-4C-alkylcarbonyl,    or-   R2 is 1-7C-alkyl substituted by R5, in which-   R5 is phenyl, R51-substituted phenyl, Har, or R52-substituted Har,    in which-   R51 is 1-4C-alkoxy,-   Har is attached to the parent molecular group via a ring carbon    atom,    -   and is an unsaturated (aromatic) 5-membered ring comprising one        to four heteroatoms independently selected from nitrogen, oxygen        and sulfur,    -   or an unsaturated (aromatic) 6-membered ring comprising one or        two nitrogen atoms,    -   or an unsaturated (aromatic) 9-membered fused bicyclic ring        system made up of a benzene ring fused to an unsaturated        (aromatic) 5-membered ring comprising one to three heteroatoms        independently selected from nitrogen, oxygen and sulfur,    -   or an unsaturated (aromatic) 10-membered fused bicyclic ring        system made up of a benzene ring fused to an unsaturated        (aromatic) 6-membered ring comprising one or two nitrogen atoms,-   R52 is 1-4C-alkyl;    and in which-   R4 is hydrogen;    and in which    either-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in which Rba,    Rbb and Rbc are independently as originally defined in aspect 2    above,    or, particularly,-   Q is unsubstituted phenyl;    and the salts, solvates or the solvates of the salts thereof.

A special interest within the present invention refers to thosecompounds according to this invention which are included by one or, whenpossible, by more of the following special embodiments orsubembodiments:

A special embodiment (embodiment 1) of the compounds according to thisinvention includes those compounds of formula Ia or Ib, in which

-   Ra is —C(O)R1.

A subembodiment (embodiment 1a) of the compounds of embodiment 1according to this invention includes those compounds of formula Ia, inwhich

-   Ra is —C(O)R1, in which-   R1 is methyl, ethyl or propyl.

Another subembodiment (embodiment 1b) of the compounds of embodiment 1according to this invention includes those compounds of formula Ia, inwhich

-   Ra is —C(O)R1, in which-   R1 is methyl which is mono-substituted by R5, ethyl which is    mono-substituted by R5, or propyl which is mono-substituted by R5,    in which-   R5 is methoxy, ethoxy, 2-methoxyethoxy, hydroxyl, pyridyl,    pyrimidinyl, pyrazinyl, imidazolo or pyrazolo.

Compounds of embodiment 1b more worthy to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)R1, in which-   R1 is methyl which is mono-substituted by R5, or ethyl which is    mono-substituted by R5, in which-   R5 is methoxy, ethoxy, 2-methoxyethoxy, hydroxyl, pyridyl or    imidazolo.

Compounds of embodiment 1b in particular worthy to be mentioned mayinclude those compounds of formula Ia, in which

-   Ra is —C(O)R1, in which-   R1 is methoxy-methyl, 2-methoxy-ethyl, (2-methoxyethoxy)-methyl,    2-(2-methoxyethoxy)-ethyl, hydroxy-methyl, 2-hydroxy-ethyl,    (pyridin-2-yl)-methyl, (pyridin-3-yl)-methyl, (pyridin-4-yl)-methyl,    2-(pyridin-2-yl)-ethyl, 2-(pyridin-3-yl)-ethyl or    2-(pyridin-4-yl)-ethyl.

Another subembodiment (embodiment 1c) of the compounds of embodiment 1according to this invention includes those compounds of formula Ia, inwhich

-   Ra is —C(O)R1, in which-   R1 is 2,3-dihydroxypropyl.

Other compounds of embodiment 1 to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)R1, in which-   R1 is 1-7C-alkyl, such as e.g. methyl, ethyl, propyl or butyl.

Other compounds of embodiment 1 to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)R1, in which-   R1 is methyl.

Other compounds of embodiment 1 to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)R1, in which-   R1 is propyl.

Another special embodiment (embodiment 2) of the compounds according tothis invention includes those compounds of formula Ia or Ib, in which

-   Ra is —C(O)OR2.

A subembodiment (embodiment 2a) of the compounds of embodiment 1according to this invention includes those compounds of formula Ia, inwhich

-   Ra is —C(O)OR2, in which-   R2 is methyl, ethyl or propyl.

Compounds of embodiment 2a more worthy to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)OR2, in which-   R2 is ethyl.

Another subembodiment (embodiment 2b) of the compounds of embodiment 1according to this invention includes those compounds of formula Ia, inwhich

-   Ra is —C(O)OR2, in which    either-   R2 is methyl which is mono-substituted by R5, ethyl which is    mono-substituted by R5, or propyl which is mono-substituted by R5,    in which-   R5 is pyridyl, pyrimidinyl or pyrazinyl.    or-   R2 is ethyl which is mono-substituted by R5, or propyl which is    mono-substituted by R5, in which-   R5 is methoxy, ethoxy, 2-methoxyethoxy, hydroxyl, imidazolo or    pyrazolo.

Compounds of embodiment 2b more worthy to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)OR2, in which    either-   R2 is methyl which is mono-substituted by R5, or ethyl which is    mono-substituted by R5, in which-   R5 is pyridyl,    or-   R2 is ethyl which is mono-substituted by R5, in which-   R5 is methoxy, ethoxy, 2-methoxyethoxy, hydroxyl or imidazolo.

Compounds of embodiment 2b in particular worthy to be mentioned mayinclude those compounds of formula Ia, in which

-   Ra is —C(O)OR2, in which-   R2 is 2-methoxy-ethyl, 2-(2-methoxyethoxy)-ethyl, 2-hydroxy-ethyl,    (pyridin-2-yl)-methyl, (pyridin-3-yl)-methyl, (pyridin-4-yl)-methyl,    2-(pyridin-2-yl)-ethyl, 2-(pyridin-3-yl)-ethyl or    2-(pyridin-4-yl)-ethyl.

Another subembodiment (embodiment 2c) of the compounds of embodiment 1according to this invention includes those compounds of formula Ia, inwhich

-   Ra is —C(O)OR2, in which-   R2 is 2,3-dihydroxypropyl.

Other compounds of embodiment 2 to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)OR2, in which-   R2 is 1-7C-alkyl, such as e.g. methyl, ethyl, tertbutyl, pentyl or    hexyl.

Other compounds of embodiment 2 to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)OR2, in which-   R2 is methyl.

Other compounds of embodiment 2 to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)OR2, in which-   R2 is butyl.

Other compounds of embodiment 2 to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)OR2, in which-   R2 is phenyl-1-4C-alkyl, such as e.g. phenethyl or benzyl.

Other compounds of embodiment 2 to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)OR2, in which-   R2 is phenethyl.

Other compounds of embodiment 2 to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)OR2, in which-   R2 is phenyl, or    -   R5-substituted phenyl, such as e.g. 3-(R5)-phenyl, in which-   R5 is 1-4C-alkoxy, such as e.g. methoxy.

Other compounds of embodiment 2 to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)OR2, in which-   R2 is phenyl.

Other compounds of embodiment 2 to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)OR2, in which-   R2 is 3-methoxy-phenyl.

Another special embodiment (embodiment 3) of the compounds according tothis invention includes those compounds of formula Ia or Ib, in which

-   Ra is —C(O)SR2.

A subembodiment (embodiment 3a) of the compounds of embodiment 1according to this invention includes those compounds of formula Ia, inwhich

-   Ra is —C(O)SR2, in which-   R2 is methyl, ethyl or propyl.

Compounds of embodiment 3a more worthy to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)SR2, in which-   R2 is ethyl.

Another subembodiment (embodiment 3b) of the compounds of embodiment 1according to this invention includes those compounds of formula Ia, inwhich

-   Ra is —C(O)SR2, in which    either-   R2 is methyl which is mono-substituted by R5, ethyl which is    mono-substituted by R5, or propyl which is mono-substituted by R5,    in which-   R5 is pyridyl, pyrimidinyl or pyrazinyl.    or-   R2 is ethyl which is mono-substituted by R5, or propyl which is    mono-substituted by R5, in which-   R5 is methoxy, ethoxy, 2-methoxyethoxy, hydroxyl, imidazolo or    pyrazolo.

Compounds of embodiment 3b more worthy to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)SR2, in which    either-   R2 is methyl which is mono-substituted by R5, or ethyl which is    mono-substituted by R5, in which-   R5 is pyridyl,    or-   R2 is ethyl which is mono-substituted by R5, in which-   R5 is methoxy, ethoxy, 2-methoxyethoxy, hydroxyl or imidazolo.

Compounds of embodiment 3b in particular worthy to be mentioned mayinclude those compounds of formula Ia, in which

-   Ra is —C(O)SR2, in which-   R2 is 2-methoxy-ethyl, 2-(2-methoxyethoxy)-ethyl, 2-hydroxy-ethyl,    (pyridin-2-yl)-methyl, (pyridin-3-yl)-methyl, (pyridin-4-yl)-methyl,    2-(pyridin-2-yl)-ethyl, 2-(pyridin-3-yl)-ethyl or    2-(pyridin-4-yl)-ethyl.

Other compounds of embodiment 3 to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)SR2, in which-   R2 is 1-7C-alkyl, such as e.g. ethyl.

Another special embodiment (embodiment 4) of the compounds according tothis invention includes those compounds of formula Ia or Ib, in which

-   Ra is —C(O)N(R3)R4;

Other compounds of embodiment 4 to be mentioned may include thosecompounds of formula Ia, in which

-   Ra is —C(O)N(R3)R4, in which-   R3 is 1-7C-alkyl, such as e.g. ethyl,-   R4 is hydrogen.

Another special embodiment (embodiment 5) of the compounds according tothis invention includes those compounds of formula Ia or Ib, in which

-   Ra is —S(O)₂R1.

Another special embodiment (embodiment 6) of the compounds according tothis invention includes those compounds of formula Ia or Ib, in which

-   Ra is —S(O)₂N(R3)R4.

Among these aforementioned embodiments, the embodiments 1, 2 and 3 areto be emphasized.

Another special embodiment (embodiment 7) of the compounds according tothis invention includes those compounds of formula Ia or Ib, in which

-   Q is unsubstituted phenyl.

Particular compounds of embodiment 7 may include those compounds offormula Ia, in which

-   Q is unsubstituted phenyl.

Another special embodiment (embodiment 8) of the compounds according tothis invention includes those compounds of formula Ia or Ib, in which

-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl.

Compounds of embodiment 8 worthy to be mentioned may include thosecompounds of formula Ia, in which

-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in which-   Rba is halogen, 1-4C-alkyl, nitro, trifluoromethyl, 1-4C-alkoxy,    di-1-4C-alkylamino, hydroxyl, 1-4C-alkylcarbonyloxy, cyano, phenyl,    morpholino, phenoxy, or completely or predominantly    fluorine-substituted 1-4C-alkoxy,-   Rbb is 1-4C-alkoxy, halogen or 1-4C-alkyl,-   Rbc is halogen.

Compounds of embodiment 8 more worthy to be mentioned may include thosecompounds of formula Ia, in which

-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in which-   Rba is chlorine, fluorine, bromine, methyl, ethyl, nitro, methoxy,    ethoxy, isopropyloxy, propoxy, hydroxyl, methylcarbonyloxy, cyano,    morpholino, difluoromethoxy or trifluoromethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine or methyl,-   Rbc is fluorine.

Compounds of embodiment 8 further more worthy to be mentioned mayinclude those compounds of formula Ia, in which

-   Q is Rba-substituted phenyl, in which-   Rba is chlorine, fluorine, bromine, methyl, ethyl, nitro, methoxy,    ethoxy, isopropyloxy, propoxy, hydroxyl, methylcarbonyloxy, cyano,    morpholino, difluoromethoxy or trifluoromethoxy.

Yet compounds of embodiment 8 further more worthy to be mentioned mayinclude those compounds of formula Ia, in which

-   Q is Rba- and Rbb-substituted phenyl, in which-   Rba is chlorine, fluorine, bromine, methyl, methoxy or ethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine or methyl.

Yet compounds of embodiment 8 further more worthy to be mentioned mayinclude those compounds of formula Ia, in which

-   Q is Rba- and Rbb- and Rbc-substituted phenyl, in which-   Rba is chlorine, fluorine, bromine, methyl, methoxy or ethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine or methyl,-   Rbc is fluorine.

Compounds of embodiment 8 in particular worthy to be mentioned mayinclude those compounds of formula Ia, in which

-   Q is 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl,    2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-ethoxyphenyl,    3-ethoxyphenyl, 4-ethoxyphenyl, 2-methylphenyl, 3-methylphenyl,    4-methylphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl,    2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl,-   2-acetoxyphenyl, 2-bromophenyl, 2-ethylphenyl, 2-cyanophenyl,    2-morpholinophenyl, 2-isopropoxyphenyl, 2-propoxyphenyl,    2-difluoromethoxyphenyl or 2-trifluoromethoxyphenyl.

Yet compounds of embodiment 8 in particular worthy to be mentioned mayinclude those compounds of formula Ia, in which

-   Q is substituted by Rbb, and is 2-methoxyphenyl, 3-methoxyphenyl,    4-methoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl,    2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-methylphenyl,    3-methylphenyl, 4-methylphenyl, 2-fluorophenyl, 3-fluorophenyl,    4-fluorophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl,    2-acetoxyphenyl, 2-bromophenyl, 2-ethylphenyl, 2-cyanophenyl,    2-morpholinophenyl, 2-isopropoxyphenyl, 2-propoxyphenyl,    2-difluoromethoxyphenyl or 2-trifluoromethoxyphenyl, in which-   Rbb is methoxy, chlorine, fluorine or methyl;    such as e.g.-   Q is any one selected from 2,3-difluorophenyl,    2-fluoro-3-chlorophenyl, 2-fluoro-4-chlorophenyl,    2-chloro-6-fluorophenyl, 2,6-dichlorophenyl, 2,4-dichlorophenyl,    2,6-difluorophenyl, 2-fluoro-4-methoxyphenyl,    2-methyl-5-fluorophenyl, 2-methyl-3-fluorophenyl,    2-methyl-4-fluorophenyl, 2,3-dimethylphenyl, 2,3-dimethoxyphenyl,    2-ethoxy-3-methoxyphenyl, 2,5-dimethoxyphenyl and    2,6-dimethoxyphenyl.

Yet compounds of embodiment 8 in particular worthy to be mentioned mayinclude those compounds of formula Ia, in which

-   Q is substituted by Rbb and Rbc, and is 2-methoxyphenyl,    3-methoxyphenyl, 4-methoxyphenyl, 2-chlorophenyl, 3-chlorophenyl,    4-chlorophenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl,    2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-fluorophenyl,    3-fluorophenyl, 4-fluorophenyl, 2-nitrophenyl, 3-nitrophenyl,    4-nitrophenyl, 2-acetoxyphenyl, 2-bromophenyl, 2-ethylphenyl,    2-cyanophenyl, 2-morpholinophenyl, 2-isopropoxyphenyl,    2-propoxyphenyl, 2-difluoromethoxyphenyl or    2-trifluoromethoxyphenyl, in which-   Rbb is methoxy, chlorine, fluorine or methyl,-   Rbc is fluorine;    such as e.g.-   Q is any one selected from 2-chloro-3,6-difluorophenyl and    2,3,6-trifluorophenyl.

Compounds of embodiment 8 in more particular worthy to be mentioned mayinclude those compounds of formula Ia, in which

-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in which-   Rba is chlorine, fluorine, methyl, ethyl, methoxy, ethoxy,    difluoromethoxy or trifluoromethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine or methyl,-   Rbc is fluorine.

Compounds of embodiment 8 to be emphasized may include those compoundsof formula Ia, in which

-   Q is Rba-substituted phenyl, in which-   Rba is chlorine, fluorine, methyl, ethyl, methoxy, ethoxy,    difluoromethoxy or trifluoromethoxy, especially-   Rba is chlorine, methyl, methoxy or ethoxy.

Yet compounds of embodiment 8 to be emphasized may include thosecompounds of formula Ia, in which

-   Q is Rba- and Rbb-substituted phenyl, in which-   Rba is chlorine, fluorine, methyl, methoxy or ethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine or methyl,    especially-   Rba is chlorine, methyl, methoxy or ethoxy,-   Rbb is methoxy, chlorine, fluorine or methyl.

Yet compounds of embodiment 8 to be emphasized may include thosecompounds of formula Ia, in which

-   Q is Rba- and Rbb- and Rbc-substituted phenyl, in which-   Rba is chlorine, fluorine, methyl, methoxy or ethoxy,-   Rbb is methoxy, ethoxy, fluorine, chlorine or methyl,-   Rbc is fluorine,    especially-   Rba is chlorine, methyl, methoxy or ethoxy,-   Rbb is methoxy, chlorine, fluorine or methyl,-   Rbc is fluorine.

Compounds of embodiment 8 to be more emphasized may include thosecompounds of formula Ia, in which

-   Q is any one selected from 2-methoxyphenyl, 3-methoxyphenyl,    4-methoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl,    2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-methylphenyl,    3-methylphenyl, 4-methylphenyl, 2-fluorophenyl, 3-fluorophenyl,    4-fluorophenyl, 2-ethylphenyl, 2-difluoromethoxyphenyl and    2-trifluoromethoxyphenyl.

Compounds of embodiment 8 to be more emphasized may include thosecompounds of formula Ia, in which

-   Q is any one selected from 2,3-difluorophenyl,    2-fluoro-3-chlorophenyl, 2-fluoro-4-chlorophenyl,    2-chloro-6-fluorophenyl, 2,6-dichlorophenyl, 2,4-dichlorophenyl,    2,6-difluorophenyl, 2-fluoro-4-methoxyphenyl,    2-methyl-5-fluorophenyl, 2-methyl-3-fluorophenyl,    2-methyl-4-fluorophenyl, 2,3-dimethylphenyl, 2,3-dimethoxyphenyl,    2-ethoxy-3-methoxyphenyl, 2,5-dimethoxyphenyl and    2,6-dimethoxyphenyl.

Compounds of embodiment 8 to be in particular emphasized may includethose compounds of formula Ia, in which

-   Q is 2-methoxyphenyl, 2-chlorophenyl, 2-ethoxyphenyl or    2-methylphenyl.

Yet compounds of embodiment 8 to be in particular emphasized may includethose compounds of formula Ia, in which

-   Q is 2-(Rba)-3-(Rbb)-phenyl, in which-   Rba is chlorine, methoxy, ethoxy or methyl,-   Rbb is methoxy, chlorine or methyl,    such as e.g.-   Q is 2,3-dimethylphenyl, 2,3-dimethoxyphenyl or    2-ethoxy-3-methoxyphenyl.

Yet compounds of embodiment 8 to be in particular emphasized may includethose compounds of formula Ia, in which

-   Q is 2-(Rba)-5-(Rbb)-phenyl, in which-   Rba is chlorine, methoxy, ethoxy or methyl,-   Rbb is methoxy, chlorine or methyl,    such as e.g.-   Q is 2,5-dimethoxyphenyl.

Compounds of embodiment 8 to be in more particular emphasized mayinclude those compounds of formula Ia, in which

-   Q is 2-methoxyphenyl or 2-ethoxyphenyl.

Yet compounds of embodiment 8 to be in more particular emphasized mayinclude those compounds of formula Ia, in which

-   Q is 2-(Rba)-3-(Rbb)-phenyl, in which-   Rba is methoxy or ethoxy,-   Rbb is methoxy or methyl.

Yet compounds of embodiment 8 to be in more particular emphasized mayinclude those compounds of formula Ia, in which

-   Q is 2-(Rba)-5-(Rbb)-phenyl, in which-   Rba is methoxy or ethoxy,-   Rbb is methoxy or methyl.

Compounds of embodiment 8 to be in further more particular emphasizedmay include those compounds of formula Ia, in which

-   Q is 2-(Rba)-5-(Rbb)-phenyl, in which-   Rba is methoxy,-   Rbb is methoxy or methyl.

Yet compounds of embodiment 8 to be in further more particularemphasized may include those compounds of formula Ia, in which

-   Q is 2-(Rba)-5-(Rbb)-phenyl, in which-   Rba is ethoxy,-   Rbb is methoxy or methyl.

Particular compounds of embodiment 8 may include those compounds offormula Ia, in which

-   Q is 2-methoxyphenyl.

Yet particular compounds of embodiment 8 may include those compounds offormula Ia, in which

-   Q is 2,3-dimethoxyphenyl.

Yet particular compounds of embodiment 8 may include those compounds offormula Ia, in which

-   Q is 2-ethoxy-3-methoxy-phenyl.

Yet particular compounds of embodiment 8 may include those compounds offormula Ia, in which

-   Q is 2-ethoxy-3-methyl-phenyl.

Yet particular compounds of embodiment 8 may include those compounds offormula Ia, in which

-   Q is 2,5-dimethoxyphenyl.

Yet particular compounds of embodiment 8 may include those compounds offormula Ia, in which

-   Q is 2-methoxy-5-methyl-phenyl.

More particular compounds of embodiment 8 may include those compounds offormula Ia, in which

-   Q is 2-ethoxyphenyl.

Yet more particular compounds of embodiment 8 may include thosecompounds of formula Ia, in which

-   Q is 2-ethoxy-5-methoxy-phenyl.

Yet more particular compounds of embodiment 8 may include thosecompounds of formula Ia, in which

-   Q is 2-ethoxy-5-methyl-phenyl.

Other compounds of embodiment 8 to be mentioned may include thosecompounds of formula Ia, in which

-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in which-   Rba is halogen, 1-4C-alkyl, nitro, trifluoromethyl, or 1-4C-alkoxy,-   Rbb is 1-4C-alkoxy, or halogen,-   Rbc is 1-4C-alkoxy.

Other compounds of embodiment 8 to be mentioned may include thosecompounds of formula Ia, in which

-   Q is Rba- and/or Rbb-substituted phenyl, in which-   Rba is halogen, nitro, 1-4C-alkyl, 1-4C-alkoxy, or trifluoromethyl,-   Rbb is 1-4C-alkoxy, or halogen.

Other compounds of embodiment 8 to be mentioned may include thosecompounds of formula Ia, in which

-   Q is Rba-substituted phenyl, in which-   Rba is halogen, nitro, 1-4C-alkyl, 1-4C-alkoxy, or trifluoromethyl;    in particular-   Rba is fluorine, chlorine, methyl, nitro, trifluoromethyl, or    methoxy.

Other compounds of embodiment 8 to be mentioned may include thosecompounds of formula Ia, in which

-   Q is Rba- and Rbb-substituted phenyl, in which-   Rba is 1-4C-alkoxy, or halogen particularly chlorine,-   Rbb is 1-4C-alkoxy, or halogen particularly chlorine; such as, for    example,-   Q is di-1-4C-alkoxy-phenyl particularly di-methoxy-phenyl, or    di-chloro-phenyl.

Other compounds of embodiment 8 to be mentioned may include thosecompounds of formula Ia, in which

-   Q is 2-chloro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl,    2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl,    2-trifluoromethyl-phenyl, 2-nitro-phenyl, 3-nitro-phenyl,    2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-methoxy-phenyl,    4-methoxy-phenyl, 2,3-dimethoxy-phenyl, or 2,4-dichloro-phenyl.

Other compounds of embodiment 8 to be mentioned may include thosecompounds of formula Ia, in which

-   Q is 2-chloro-phenyl, 3-chloro-phenyl, 3-fluoro-phenyl,    2-trifluoromethyl-phenyl, 2-nitro-phenyl, 3-nitro-phenyl,    2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-methoxy-phenyl,    4-methoxy-phenyl, 2,3-dimethoxy-phenyl, or 2,4-dichloro-phenyl.

Another special embodiment (embodiment 9) of the compounds according tothis invention includes those compounds of formula Ia or Ib, in which

-   Q is optionally substituted by Rca and/or Rcb, and is Har.

Compounds of embodiment 9 worthy to be mentioned may include thosecompounds of formula Ia, in which

-   Q is optionally substituted by Rca, and is Har, in which-   Rca is methyl, ethyl or chlorine,-   Har is furanyl, such as e.g. furan-2-yl or furan-3-yl.

Particular compounds of embodiment 9 may include those compounds offormula Ia, in which

-   Q is unsubstituted Har, in which-   Har is furanyl, such as e.g. furan-2-yl or furan-3-yl.

Yet particular compounds of embodiment 9 may include those compounds offormula Ia, in which

-   Q is unsubstituted Har, in which-   Har is thiophenyl, such as e.g. thiophen-2-yl or thiophen-3-yl.

Yet particular compounds of embodiment 9 may include those compounds offormula Ia, in which

-   Q is unsubstituted Har, in which-   Har is pyridyl, such as e.g. pyridin-2-yl, pyridin-4-yl or,    especially, pyridin-3-yl.

More particular compounds of embodiment 9 may include those compounds offormula Ia, in which

-   Q is unsubstituted Har, in which-   Har is pyridin-3-yl.

Another special embodiment (embodiment 10) of the compounds according tothis invention includes those compounds of formula Ia or Ib, in which

-   Q is Cyc.

Compounds of embodiment 10 worthy to be mentioned may include thosecompounds of formula Ia, in which

-   Q is Cyc, in which-   Cyc is optionally substituted by halogen on its benzene ring, and is    1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl,    2,2-difluoro-1,3-benzodioxolyl or 2,3-dihydro-furanyl, whereby said    Cyc ring system is attached to the parent molecular group via a    substitutable benzoring carbon atom.

Compounds of embodiment 10 more worthy to be mentioned may include thosecompounds of formula Ia, in which

-   Q is Cyc, in which-   Cyc is optionally substituted by bromine on its benzene ring, and is    1,3-benzodioxol-4-yl, 1,3-benzodioxol-5-yl,    2,2-difluoro-1,3-benzodioxol-4-yl or    2,2-difluoro-1,3-benzodioxol-5-yl.

Compounds of embodiment 10 in particular worthy to be mentioned mayinclude those compounds of formula Ia, in which

-   Q is Cyc, in which-   Cyc is 1,3-benzodioxol-4-yl or 2,2-difluoro-1,3-benzodioxol-4-yl.

Particular compounds of embodiment 10 may include those compounds offormula Ia, in which

-   Q is Cyc, in which-   Cyc is 1,3-benzodioxol-4-yl.

Other compounds of embodiment 10 to be mentioned may include thosecompounds of formula Ia, in which

Q is 1,3-benzodioxol-5-yl, 2,3-dihydro-1,4-benzodioxin-6-yl,2,3-dihydro-furan-5-yl, or 2,3-dihydro-furan-6-yl.

Other compounds of embodiment 10 to be mentioned may include thosecompounds of formula Ia, in which

-   Q is 1,3-benzodioxol-5-yl, or 2,3-dihydro-1,4-benzodioxin-6-yl.

Another special embodiment (embodiment 11) of the compounds according tothis invention includes those compounds of formula Ia.

A group of compounds according to special embodiment 1 of the compoundsaccording to this invention may include those compounds of formula Ia orIb, in which

-   Ra is —C(O)R1,    in which R1 is a radical selected from the following List 1.    List 1 consists of the following radicals:

Another group of compounds according to this invention may include thosecompounds of formula Ia, in which

-   Q is unsubstituted phenyl, and-   Ra is —C(O)R1,    in which R1 is a radical selected from the List 1.

Another group of compounds according to this invention may include thosecompounds of formula Ia, in which

-   Q is 2-chloro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl,    2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl,    2-trifluoromethyl-phenyl, 2-nitro-phenyl, 3-nitro-phenyl,    2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-methoxy-phenyl,    4-methoxy-phenyl, 2,3-dimethoxy-phenyl, or 2,4-dichloro-phenyl, and-   Ra is —C(O)R1,    in which R1 is a radical selected from the List 1.

Another group of compounds according to this invention may include thosecompounds of formula Ia, in which

-   Q is thiophenyl, furanyl, or pyridyl, and-   Ra is —C(O)R1,    in which R1 is a radical selected from the List 1.

Another group of compounds according to this invention may include thosecompounds of formula Ia, in which

-   Q is any one selected from 2-methoxyphenyl, 3-methoxyphenyl,    4-methoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl,    2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-methylphenyl,    3-methylphenyl, 4-methylphenyl, 2-fluorophenyl, 3-fluorophenyl,    4-fluorophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl,    2-acetoxyphenyl, 2-bromophenyl, 2-ethylphenyl, 2-cyanophenyl,    2-morpholinophenyl, 2-isopropoxyphenyl, 2-propoxyphenyl,    2-difluoromethoxyphenyl, 2-trifluoromethoxyphenyl,    2,3-difluorophenyl, 2-fluoro-3-chlorophenyl,    2-fluoro-4-chlorophenyl, 2-chloro-6-fluorophenyl,    2,6-dichlorophenyl, 2,4-dichlorophenyl, 2,6-difluorophenyl,    2-fluoro-4-methoxyphenyl, 2-methyl-5-fluorophenyl,    2-methyl-3-fluorophenyl, 2-methyl-4-fluorophenyl,    2,3-dimethylphenyl, 2,3-dimethoxyphenyl, 2-ethoxy-3-methoxyphenyl,    2,5-dimethoxyphenyl and 2,6-dimethoxyphenyl,-   Ra is —C(O)R1,    in which R1 is a radical selected from the List 1.

A group of compounds according to special embodiment 2 of the compoundsaccording to this invention may include those compounds of formula Ia orIb, in which

-   Ra is —C(O)OR2,    in which R2 is a radical selected from the following List 2.

List 2 consists of the following radicals:

Another group of compounds according to this invention may include thosecompounds of formula Ia, in which

-   Q is unsubstituted phenyl, and-   Ra is —C(O)OR2,    in which R2 is a radical selected from the List 2.

Another group of compounds according to this invention may include thosecompounds of formula Ia, in which

-   Q is 2-chloro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl,    2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl,    2-trifluoromethyl-phenyl, 2-nitro-phenyl, 3-nitro-phenyl,    2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-methoxy-phenyl,    4-methoxy-phenyl, 2,3-dimethoxy-phenyl, or 2,4-dichloro-phenyl, and-   Ra is —C(O)OR2,    in which R2 is a radical selected from the List 2.

Another group of compounds according to this invention may include thosecompounds of formula Ia, in which

-   Q is thiophenyl, furanyl, or pyridyl, and-   Ra is —C(O)OR2,    in which R2 is a radical selected from the List 2.

Another group of compounds according to this invention may include thosecompounds of formula Ia, in which

-   Q is any one selected from 2-methoxyphenyl, 3-methoxyphenyl,    4-methoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl,    2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-methylphenyl,    3-methylphenyl, 4-methylphenyl, 2-fluorophenyl, 3-fluorophenyl,    4-fluorophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl,    2-acetoxyphenyl, 2-bromophenyl, 2-ethylphenyl, 2-cyanophenyl,    2-morpholinophenyl, 2-isopropoxyphenyl, 2-propoxyphenyl,    2-difluoromethoxyphenyl, 2-trifluoromethoxyphenyl,    2,3-difluorophenyl, 2-fluoro-3-chlorophenyl,    2-fluoro-4-chlorophenyl, 2-chloro-6-fluorophenyl,    2,6-dichlorophenyl, 2,4-dichlorophenyl, 2,6-difluorophenyl,    2-fluoro-4-methoxyphenyl, 2-methyl-5-fluorophenyl,    2-methyl-3-fluorophenyl, 2-methyl-4-fluorophenyl,    2,3-dimethylphenyl, 2,3-dimethoxyphenyl, 2-ethoxy-3-methoxyphenyl,    2,5-dimethoxyphenyl and 2,6-dimethoxyphenyl,-   Ra is —C(O)OR2,    in which R2 is a radical selected from the List 2.

A group of compounds according to special embodiment 3 of the compoundsaccording to this invention may include those compounds of formula Ia orIb, in which

-   Ra is —C(O)SR2,    in which R2 is a radical selected from the following List 3.

List 3 consists of the following radicals:

Another group of compounds according to this invention may include thosecompounds of formula Ia, in which

-   Q is unsubstituted phenyl, and-   Ra is —C(O)SR2,    in which R2 is a radical selected from the List 3.

Another group of compounds according to this invention may include thosecompounds of formula Ia, in which

-   Q is 2-chloro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl,    2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl,    2-trifluoromethyl-phenyl, 2-nitro-phenyl, 3-nitro-phenyl,    2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-methoxy-phenyl,    4-methoxy-phenyl, 2,3-dimethoxy-phenyl, or 2,4-dichloro-phenyl, and-   Ra is —C(O)SR2,    in which R2 is a radical selected from the List 3.

Another group of compounds according to this invention may include thosecompounds of formula Ia, in which

-   Q is thiophenyl, furanyl, or pyridyl, and-   Ra is —C(O)SR2,    in which R2 is a radical selected from the List 3.

Another group of compounds according to this invention may include thosecompounds of formula Ia, in which

-   Q is any one selected from 2-methoxyphenyl, 3-methoxyphenyl,    4-methoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl,    2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-methylphenyl,    3-methylphenyl, 4-methylphenyl, 2-fluorophenyl, 3-fluorophenyl,    4-fluorophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl,    2-acetoxyphenyl, 2-bromophenyl, 2-ethylphenyl, 2-cyanophenyl,    2-morpholinophenyl, 2-isopropoxyphenyl, 2-propoxyphenyl,    2-difluoromethoxyphenyl, 2-trifluoromethoxyphenyl,    2,3-difluorophenyl, 2-fluoro-3-chlorophenyl,    2-fluoro-4-chlorophenyl, 2-chloro-6-fluorophenyl,    2,6-dichlorophenyl, 2,4-dichlorophenyl, 2,6-difluorophenyl,    2-fluoro-4-methoxyphenyl, 2-methyl-5-fluorophenyl,    2-methyl-3-fluorophenyl, 2-methyl-4-fluorophenyl,    2,3-dimethylphenyl, 2,3-dimethoxyphenyl, 2-ethoxy-3-methoxyphenyl,    2,5-dimethoxyphenyl and 2,6-dimethoxyphenyl,-   Ra is —C(O)SR2,    in which R2 is a radical selected from the List 3.

In one embodiment, compounds according to aspect 2 of this invention inparticular worthy to be noted are those compounds of formulae Ia or Ibas shown herein, in which

-   Ra is —C(O)R1, in which-   R1 is 1-5C-alkyl, phenyl, pyridyl, morpholino, indolyl, or    1-5C-alkyl which is substituted by one substituent selected from R5,    in which-   R5 is 1-4C-alkoxy, phenoxy, 1-4C-alkoxy-2-4C-alkoxy, hydroxyl,    benzyloxy, phenyl, pyridyl, indolyl, 1-4C-alkoxycarbonyl, carboxyl,    amino, di-1-4C-alkylamino, morpholino, piperidino, pyrrolidino,    4N-(1-4C-alkyl)-piperazin-1-yl, 4N—(H)-piperazin-1-yl, carbamoyl,    ureido, guanidino, imidazol-1-yl, 1N—(H)-imidazol-4-yl, or    1N-(1-4C-alkyl)-imidazol-4-yl;    or in which-   Ra is —C(O)OR2, in which    either-   R2 is 1-5C-alkyl, phenyl, pyridyl, or (1-4C-alkoxy)-phenyl,    or-   R2 is 1-5C-alkyl which is substituted by one substituent selected    from R5, in which-   R5 is phenyl, pyridyl, indolyl, 4-methyl-thiazolyl,    1-4C-alkoxycarbonyl, carboxyl, (1-4C-alkoxy)-phenyl,    -   1N—(H)-imidazol-4-yl, or 1N-(1-4C-alkyl)-imidazol-4-yl,        or-   R2 is 2-5C-alkyl which is substituted by one substituent selected    from R5, in which-   R5 is 1-4C-alkoxy, phenoxy, 1-4C-alkoxy-2-4C-alkoxy, hydroxyl,    benzyloxy, 1-4C-alkylcarbonyloxy, amino, di-1-4C-alkylamino,    1-4C-alkylcarbonylamino, morpholino, piperidino, pyrrolidino,    4N-(1-4C-alkyl)-piperazin-1-yl, 4N—(H)-piperazin-1-yl, or    imidazol-1-yl;    or in which-   Ra is —C(O)SR2, in which-   R2 is 1-5C-alkyl, or 2-5C-alkyl which is substituted by one    substituent selected from R5, in which-   R5 is 1-4C-alkoxycarbonyl, carboxyl, hydroxyl,    1-4C-alkylcarbonyloxy, di-1-4C-alkylamino, 1-4C-alkylcarbonylamino,    pyridyl or pyrazinyl;    and in which    either-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in which-   Rba is halogen, 1-4C-alkyl, nitro, trifluoromethyl, or 1-4C-alkoxy,-   Rbb is 1-4C-alkoxy, or halogen,-   Rbc is 1-4C-alkoxy,    -   such as, for example,-   Q is Rba-substituted phenyl, in which-   Rba is halogen, 1-4C-alkyl, nitro, trifluoromethyl, or 1-4C-alkoxy,    -   or-   Q is Rba- and Rbb-substituted phenyl, in which-   Rba is 1-4C-alkoxy, or halogen,-   Rbb is 1-4C-alkoxy, or halogen,    -   such as, for example,-   Q is di-(1-4C-alkoxy)-phenyl, or di-(chloro)-phenyl,    or-   Q is unsubstituted phenyl,    or-   Q is thiophenyl, furanyl, or pyridyl,    or-   Q is 1,3-benzodioxol-5-yl, or 2,3-dihydro-1,4-benzodioxin-6-yl;    in particular    either-   Q is Rba-substituted phenyl, in which-   Rba is fluorine, chlorine, methyl, nitro, trifluoromethyl, or    methoxy,    or-   Q is di-methoxy-phenyl, or di-chloro-phenyl,    or-   Q is unsubstituted phenyl,    or-   Q is thiophenyl, furanyl, or pyridyl,    or-   Q is 1,3-benzodioxol-5-yl, or 2,3-dihydro-1,4-benzodioxin-6-yl;    and the salts, solvates or the solvates of the salts thereof.

In another embodiment, compounds according to aspect 2 of this inventionin particular worthy to be noted are those compounds of formulae Ia orIb as shown herein,

in which

-   Ra is —C(O)R1, —C(O)OR2, —C(O)SR2, or —C(O)N(R3)R4;    and    either-   Q is optionally substituted by Rba and/or Rbb and/or Rbc, and is    phenyl,    or-   Q is bonded to the adjacent unsaturated group via a ring carbon    atom, and is Har,    or-   Q is Cyc;    in which    either-   R1, R2 and R3 may be the same or different and are independently    selected from: 1-7C-alkyl, and 1-7C-alkyl which is substituted by    one substituent selected from R5, in which-   R5 is 1-4C-alkoxy, phenyl, thiophenyl, furanyl, pyridyl,    methylthiazolyl, indolyl, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyl,    or carbamoyl,    or-   R1, R2 and R3 may be the same or different and are independently    selected from: phenyl, and phenyl which is substituted by one    substituent selected from R5, in which-   R5 is 1-4C-alkoxy;-   R4 is hydrogen;-   each Rba, Rbb and Rbc may be the same or different and are    independently selected from the group consisting of:    -   1-4C-alkyl, nitro,    -   halogen, trifluoromethyl,    -   —OR7 and —N(R8)R9;-   R7 and R8 may be the same or different and are 1-4C-alkyl;-   R9 is 1-4C-alkyl;-   Har is pyridyl, thiophenyl, or furanyl;-   Cyc is 1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl,    2,3-dihydrobenzothiophenyl, or 2,3-dihydrobenzofuranyl;    and the salts, solvates or the solvates of the salts thereof.

Compounds according to aspect 2 of this invention in more particularworthy to be noted are those compounds of formula Ia,

in which, in a first alternative,

-   Ra is —C(O)R1, in which,-   R1 is 1-5C-alkyl, or 1-5C-alkyl substituted by R5, in which-   R5 is 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyl, carbamoyl, or    1-4C-alkoxy,    -   or-   R5 is pyridyl, indol-2-yl, indol-3-yl or thiophenyl,    -   or-   R5 is phenyl;    or in which, in a second alternative,-   Ra is —C(O)OR2, in which,    either-   R2 is 1-5C-alkyl,    or-   R2 is 2-5C-alkyl substituted by R5, in which-   R5 is 1-4C-alkoxy,    or-   R2 is 1-5C-alkyl substituted by R5, in which-   R5 is 4-methylthiazol-5-yl, or phenyl,    or-   R2 is phenyl, or phenyl substituted by R5, in which-   R5 is 1-4C-alkoxy;    or in which, in a third alternative,-   Ra is —C(O)SR2, in which,-   R2 is 1-5C-alkyl;    and in which    either-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in which-   Rba is halogen, 1-4C-alkyl, nitro, trifluoromethyl, or 1-4C-alkoxy,-   Rbb is 1-4C-alkoxy, or halogen,-   Rbc is 1-4C-alkoxy;    or-   Q is unsubstituted phenyl;    or-   Q is thiophenyl, furanyl, or pyridyl;    or-   Q is 1,3-benzodioxol-5-yl, or 2,3-dihydro-1,4-benzodioxin-6-yl;    and the salts, solvates or the solvates of the salts thereof.

Compounds according to aspect 2 of this invention to be emphasized arethose compounds of formula Ia,

in which, in a first alternative,

-   Ra is —C(O)R1, in which,-   R1 is 1-5C-alkyl;    or in which, in a second alternative,-   Ra is —C(O)OR2, in which,-   R2 is 1-4C-alkyl, phenyl-1-4C-alkyl, phenyl, or R5-substituted    phenyl, in which-   R5 is 1-4C-alkoxy;    or in which, in a third alternative,-   Ra is —C(O)SR2, in which,-   R2 is 1-4C-alkyl;    and in which    either-   Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in which-   Rba is halogen, 1-4C-alkyl, nitro, trifluoromethyl, or 1-4C-alkoxy,-   Rbb is 1-4C-alkoxy, or halogen,-   Rbc is 1-4C-alkoxy,    -   such as, for example,-   Q is Rba-substituted phenyl, in which-   Rba is halogen, 1-4C-alkyl, nitro, trifluoromethyl, or 1-4C-alkoxy,    -   or-   Q is Rba- and Rbb-substituted phenyl, in which-   Rba is 1-4C-alkoxy, or halogen,-   Rbb is 1-4C-alkoxy, or halogen,    -   such as, for example,-   Q is di-(1-4C-alkoxy)-phenyl, or di-(chloro)-phenyl;    or-   Q is unsubstituted phenyl;    or-   Q is thiophenyl, furanyl, or pyridyl;    or-   Q is 1,3-benzodioxol-5-yl, or 2,3-dihydro-1,4-benzodioxin-6-yl;    and the salts, solvates or the solvates of the salts thereof.

Compounds according to aspect 2 of this invention to be more emphasizedare those compounds of formula Ia,

in which, in a first alternative,

-   Ra is —C(O)R1, in which-   R1 is methyl, ethyl, propyl or butyl;    or in which, in a second alternative,-   Ra is —C(O)OR2, in which    either-   R2 is methyl, ethyl, propyl or butyl,    or-   R2 is benzyl or phenethyl,    or-   R2 is phenyl or 3-methoxy-phenyl;    or in which, in a third alternative,-   Ra is —C(O)SR2, in which-   R2 is ethyl;    and in which    either-   Q is Rba-substituted phenyl, in which-   Rba is fluorine, chlorine, methyl, nitro, trifluoromethyl, or    methoxy;    or-   Q is di-methoxy-phenyl, or di-chloro-phenyl;    or-   Q is unsubstituted phenyl;    or-   Q is thiophenyl, furanyl, or pyridyl;    or-   Q is 1,3-benzodioxol-5-yl, or 2,3-dihydro-1,4-benzodioxin-6-yl;    in particular    either-   Q is 2-chloro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl,    2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl,    2-trifluoromethyl-phenyl, 2-nitro-phenyl, 3-nitro-phenyl,    2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-methoxy-phenyl,    4-methoxy-phenyl, 2,3-dimethoxy-phenyl, or 2,4-dichloro-phenyl,    or-   Q is phenyl,    or-   Q is thiophenyl, furanyl, or pyridyl,    or-   Q is 1,3-benzodioxol-5-yl;    and the salts, solvates or the solvates of the salts thereof.

Compounds according to aspect 2 of this invention to be in particularemphasized are those compounds of formula Ia,

in which, in a first alternative,

-   Ra is —C(O)R1, in which-   R1 is methyl or propyl;    or in which, in a second alternative,-   Ra is —C(O)OR2, in which-   R2 is methyl, ethyl, butyl, phenethyl or 3-methoxy-phenyl;    or in which, in a third alternative,-   Ra is —C(O)SR2, in which-   R2 is ethyl;    and in which    either-   Q is 2-chloro-phenyl, 3-chloro-phenyl, 3-fluoro-phenyl,    2-trifluoromethyl-phenyl, 2-nitro-phenyl, 3-nitro-phenyl,    2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-methoxy-phenyl,    4-methoxy-phenyl, 2,3-dimethoxy-phenyl, or 2,4-dichloro-phenyl,    or-   Q is phenyl,    or-   Q is thiophen-2-yl, thiophen-3-yl, furan-2-yl, furan-3-yl or    pyridin-3-yl,    or-   Q is 1,3-benzodioxol-5-yl;    and the salts, solvates or the solvates of the salts thereof.

Compounds according to the present invention can be prepared asdescribed below or as shown in the following reaction scheme, or asdisclosed in WO2004/024066 or, particularly, WO2004/024065, thedisclosure of which is incorporated herein, or similarly or analogouslythereto according to preparation procedures or synthesis strategiesknown to the person skilled in the art. Accordingly, compounds accordingto the present invention can be obtained as specified by way of examplein the following examples, or similarly or analogously thereto.

Thus, as shown in the reaction scheme below, a compound of formula III,in which Ra has the meanings given above, can be condensed withmalonitrile in the presence of sulfur and a suitable base, such as forexample an amine (e.g. diethyl amine or morpholine) to givecorresponding compounds of formula II in a manner known to the personskilled in the art (e.g. according to a Gewald reaction) or as describedin the following examples.

Compounds of formula III are known or can be obtained in an art-knownmanner.

Compounds of formula II can be reacted with compounds of formulaRb—C(O)—X, in which Rb has the meanings mentioned above and X is asuitable leaving group, preferably a chlorine atom, in an acylationreaction under conditions habitual per se to give the desired compoundsof formula I, in which Ra and Rb have the meanings given above.

Alternatively, compounds of the formula I can also be prepared from thecorresponding compounds of formula II and corresponding compounds offormula Rb—C(O)—X, in which X is hydroxyl, by reaction with amide bondlinking reagents known to the person skilled in the art. Exemplary amidebond linking reagents known to the person skilled in the art which maybe mentioned are, for example, the carbodiimides (e.g.dicyclohexylcarbodiimide or, preferably,1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride),azodicarboxylic acid derivatives (e.g. diethyl azodicarboxylate),uronium salts [e.g. O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumtetrafluoroborate orO-(benzotriazol-1yl)-N,N,N′,N′-tetramethyl-uronium-hexafluorophosphate]and N,N′-carbonyldiimidazole. In the scope of this invention preferredamide bond linking reagents are uronium salts and, particularly,carbodiimides, preferably, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimidehydrochloride (EDC).

Acid derivatives of formula Rb—C(O)—X are known, commercially availableor can be prepared as it is known for the skilled person (e.g. byactivation of the corresponding carboxylic acids), or the acrylic acidderivatives are obtained according to art-known procedures, e.g. viaCC-bond coupling reactions, like a Knoevenagel or Heck reaction,starting from the appropriate starting compounds.

Optionally, compounds of formula I prepared by the processes describedherein can be converted into their salts, or, optionally, salts of thecompounds of formula I obtained can be converted into the freecompounds. Corresponding processes are known to the person skilled inthe art.

In addition, the compounds of formula I can be converted by art-knownderivatization into further compounds of formula I.

In an alternative synthesis route, compounds of formula VI, in which PGis a suitable temporary protective group, such as for exampletertbutoxycarbonyl (Boc) or one of those mentioned in “Protective Groupsin Organic Synthesis” by T. Greene and P. Wuts (John Wiley & Sons, Inc.1999, 3^(rd) Ed.) or in “Protecting Groups (Thieme Foundations OrganicChemistry Series N Group” by P. Kocienski (Thieme Medical Publishers,2000), can be condensed with malonitrile in the presence of sulfur and asuitable base as described above to give corresponding compounds offormula V.

Compounds of formula VI are known or can be obtained in an art-knownmanner.

Compounds of formula V can be acylated with compounds of formulaRb—C(O)—X analogously as mentioned above. Optionally, said amide bondformation can be obtained under microwave assistance. Subsequentialdeprotection of the protective group PG in a manner customary per se forthe skilled person gives compounds of formula IV, in which Rb has themeanings as mentioned above.

Compounds of formula IV can be converted into desired compounds offormula I by introduction of the group Ra via methods known to one ofordinary skill in the art.

More specifically, for example, compounds of the formula I, in which

-   a) Ra is an acyl group, can be prepared from compounds of formula IV    by acylation reaction;-   b) Ra is a sulfonyl group, can be obtained from compounds of formula    IV by sulfonylation reaction;-   c) Ra is an ester group, can be obtained from compounds of formula    IV by carbamate formation reaction;-   d) Ra is an amide group, can be prepared from compounds of formula    IV by urea formation reaction;-   e) Ra is a thioester group, can be prepared from compounds of    formula IV by thiocarbamate formation reaction;-   f.) Ra is a sulfonamide group, can be prepared from compounds of    formula IV by sulfamide formation reaction.

The methods mentioned under a) to f) are expediently carried outanalogously to the methods known to the person skilled in the art or asdescribed by way of example in the following examples.

The appropriate starting compounds used in the methods mentioned undera) to f) are art-known or can be obtained according to art-knownprocedures.

Optionally, compounds of formula I can be converted into furthercompounds of formula I by methods known to one of ordinary skill in theart. More specifically, for example, from compounds of the formula I inwhich

-   i) R5 is acyloxy, such as e.g. acetoxy, the corresponding free    hydroxyl compounds can be obtained by removal of the acyl group,    such as e.g. by saponification reaction;-   ii) Het is a cyclic acetal or ketal, such as e.g. the    2,2-dimethyl-[1,3]dioxolan acetal, the corresponding free dihydroxy    compounds can be obtained by cleavage of the acetal or ketal, such    as e.g. by deacetalization reaction;-   iii) R5 is an ester group, such as e.g. methoxycarbonyl, the    corresponding free carboxyl compounds can be obtained by    deesterification reaction, such as e.g. by saponification reaction.

The methods mentioned under i) to iii) can be expediently carried outanalogously to the methods known to the person skilled in the art or asdescribed by way of example in the following examples.

It is moreover known to the person skilled in the art that if there area number of reactive centers on a starting or intermediate compound itmay be necessary to block one or more reactive centers temporarily byprotective groups in order to allow a reaction to proceed specificallyat the desired reaction center. A detailed description for the use of alarge number of proven protective groups is found, for example, in“Protective Groups in Organic Synthesis” by T. Greene and P. Wuts (JohnWiley & Sons, Inc. 1999, 3^(rd) Ed.) or in “Protecting Groups (ThiemeFoundations Organic Chemistry Series N Group” by P. Kocienski (ThiemeMedical Publishers, 2000).

The substances according to the invention are isolated and purified in amanner known per se, for example by distilling off the solvent underreduced pressure and recrystallizing the residue obtained from asuitable solvent or subjecting it to one of the customary purificationmethods, such as, for example, column chromatography on a suitablesupport material.

Salts are obtained by dissolving the free compound in a suitable solvent(e.g. a ketone, such as acetone, methyl ethyl ketone or methyl isobutylketone, an ether, such as diethyl ether, tetrahydrofuran or dioxane, achlorinated hydrocarbon, such as methylene chloride or chloroform, or alow-molecular-weight aliphatic alcohol, such as ethanol or isopropanol)which contains the desired acid or base, or to which the desired acid orbase is then added. The salts are obtained by filtering,reprecipitating, precipitating with a nonsolvent for the addition saltor by evaporating the solvent. Salts obtained can be converted into thefree compounds, which can in turn be converted into salts, byalkalization or by acidification. In this manner, pharmacologicallyunacceptable salts can be converted into pharmacologically acceptablesalts.

Suitably, the conversions mentioned in this invention can be carried outanalogously or similarly to methods which are familiar per se to theperson skilled in the art.

The person skilled in the art knows on the basis of his/her knowledgeand on the basis of those synthesis routes, which are shown anddescribed within the description of this invention, how to find otherpossible synthesis routes for compounds of formula I. All these otherpossible synthesis routes are also part of this invention.

Having described the invention in detail, the scope of the presentinvention is not limited only to those described characteristics orembodiments. As will be apparent to persons skilled in the art,modifications, analogies, variations, derivations, homologisations,alternatives and adaptations to the described invention can be made onthe base of art-known knowledge and/or, particularly, on the base of thedisclosure (e.g. the explicit, implicit or inherent disclosure) of thepresent invention without departing from the spirit and scope of thisinvention as defined by the scope of the appended claims.

The following examples serve to illustrate the invention further withoutrestricting it. Likewise, further compounds of formula I, whosepreparation is not explicitly described, can be prepared in an analogousor similar manner or in a manner familiar per se to the person skilledin the art using customary process techniques.

Any or all of the compounds of formula I according to the presentinvention which are mentioned in the following examples, particularlywhich are mentioned as final compounds, as well as their salts are apreferred subject of the present invention.

In the examples, MS stands for mass spectrum, calc. for calculated, fnd.for found, Boc for the tertbutoxycarbonyl group, and other abbreviationshave their meanings customary per se to the skilled person.

EXAMPLES

Final Compounds:

1.N-(6-Ethoxycarbonyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide

The title compound can be prepared according to general procedure Adescribed below starting from2-amino-3-cyano-4,7-dihydro-thieno[2,3-c]pyridine-6(5H)-carboxylic acidethyl ester (compound A1) and 3-phenylacrylyl chloride.

MS: Calc.: C₂₀H₁₉N₃O₃S, (381.46). Fnd.: 382.1 [M+H].

2.N-(6-tert-Butoxycarbonyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide

The title compound can be prepared according to general procedure Adescribed below starting from2-amino-3-cyano-4,7-dihydro-thieno[2,3-c]pyridine-6(5H)-carboxylic acid1,1-dimethylethyl ester (compound A2) and 3-phenylacrylyl chloride.

MS: Calc.: C₂₂H₂₃N₃O₃S, (409.51). Fnd.: 410.0 [M+H].

3.N-(6-Heptanoyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide

The title compound can be prepared according to general procedure Adescribed below starting fromN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide(compound B1) and heptanoyl chloride.

MS: Calc.: C₂₄H₂₇N₃O₂S, (421.57). Fnd.: 422.2 [M+H].

The following compounds 3 to 31 can be prepared according to generalprocedure A described below starting from2-amino-3-cyano-4,7-dihydro-thieno[2,3-c]pyridine-6(5H)-carboxylic acidethyl ester (compound_A1) and the appropriate acrylic acid derivatives,e.g., more precisely, phenyl-acrylic acid, cinnamic acid,furanyl-acrylic acid, thiophenyl-acrylic acid or pyridyl-acrylic acidderivatives.

4.N-(6-Ethoxycarbonyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-chlorophenyl)-acrylamide

MS: Calc.: C₂₀H₁₈ClN₃O₃S, (415.90). Fnd.: 416.0 [M+H].

5.N-(6-Ethoxycarbonyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(3-trifluoromethyl-phenyl)-acrylamide

MS: Calc.: C₂₁H₁₈F₃N₃O₃S, (449.46). Fnd.: 450.0 [M+H].

6.N-(6-Ethoxycarbonyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-2-methyl-3-phenyl-acrylamide

MS: Calc.: C₂₁H₂₁N₃O₃S, (395.48). Fnd.: 396.0 [M+H].

7.N-(6-Ethoxycarbonyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-pyridyl-acrylamide

MS: Calc.: C₁₉H₁₈N₄O₃S, (382.44). Fnd.: 383.1 [M+H].

8.3-Cyano-2-((E)-3-thiophen-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C18 H17 N3 O3 S2 (387.48). Fnd.: 388.1 [M+H].

9.3-Cyano-2-((E)-3-thiophen-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C18 H17 N3 O3 S2 (387.48). Fnd.: 388.1 [M+H].

10.3-Cyano-2-((E)-3-furan-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C18 H17 N3 O4 S, (371.42). Fnd.: 372 [M+H].

11.3-Cyano-2-((E)-3-furan-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C18 H17 N3 O4 S, (371.42). Fnd.: 372.1 [M+H].

12.3-Cyano-2-((E)-3-o-tolyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H21 N3 O3 S, (395.48). Fnd.: 396 [M+H].

13.2-[(E)-3-(3-Chloro-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H18 Cl N3 O3 S, (415.90). Fnd.: 416.1 [M+H].

14.3-Cyano-2-((E)-3-thiophen-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H18 N4 O5 S, (426.45). Fnd.: 427.1 [M+H].

15.3-Cyano-2-[(E)-3-(4-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H21 N3 O4 S, (411.48). Fnd.: 412.2 [M+H].

16.3-Cyano-2-((E)-3-m-tolyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H21 N3 O3 S, (395.45). Fnd.: 396 [M+H].

17.3-Cyano-2-[(E)-3-(2-fluoro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H18 F N3 O3 S, (399.45). Fnd.: 400.1 [M+H].

18.3-Cyano-2-[(E)-3-(4-fluoro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H18 F N3 O3 S, (399.45). Fnd.: 400.1 [M+H].

19.3-Cyano-2-[(E)-3-(3-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H21 N3 O4 S, (411.48). Fnd.: 412.1 [M+H].

20.3-Cyano-2-[(E)-3-(2,3-dimethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C22 H23 N3 O5 S, (441.51). Fnd.: 442.1 [M+H].

21.3-Cyano-2-[(E)-3-(3-fluoro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H18 FN3 O3 S, (399.45). Fnd.: 400.1 [M+H].

22.2-[(E)-3-(4-Chloro-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H18 Cl N3 O3 S, (415.90). Fnd.: 416.1 [M+H].

23.3-Cyano-2-[(E)-3-(2-trifluoromethyl-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H18 F3 N3O3 S, (449.46). Fnd.: 450.1 [M+H].

24.3-Cyano-2-[(E)-3-(2-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H21 N3 O4 S, (411.48). Fnd.: 412.2 [M+H].

25.3-Cyano-2-[(E)-3-(4-nitro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H18 N4 O5 S, (426.45). Fnd.: 427.1 [M+H].

26.3-Cyano-2-[(E)-3-(4-dimethylamino-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C22 H24 N4 O3 S, (424.53). Fnd.: 425.1 [M+H].

27.3-Cyano-2-((E)-3-p-tolyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H21 N3 O3 S, (395.48). Fnd.: 396.1 [M+H].

28.3-Cyano-2-[(E)-3-(2,4-dichloro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H17 Cl2 N3 O3 S, (450.35). Fnd.: 450.1 [M+H].

29.3-Cyano-2-[(E)-3-(3-nitro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H18 N4 O5 S, (426.45). Fnd.: 427.1 [M+H].

30.2-((E)-3-Benzo[1,3]dioxol-5-yl-allanoylamino)-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H19 N3 O5 S, (425.47). Fnd.: 426.1 [M+H].

31. 3-Cyano-2-[(E)—(2,3,4-trimethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C23 H25 N3 O6 S, (471.54). Fnd.: 472 [M+H].

The following compound 32 can be prepared according to general procedureA described below starting from2-amino-3-cyano-4,7-dihydro-thieno[2,3-c]pyridine-6(5H)-carboxylic acid1,1-dimethylethyl ester (compound A2) and the pyridyl-acrylic acidchloride.

32.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid tert-butyl ester

MS: Calc.: C21 H22 N4 O3 S, (410.5). Fnd.: 411 [M+H].

The following compounds 33 and 34 can be prepared according to generalprocedure A described below starting fromN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide(compound B1) and butanoyl chloride, or, respectively, acetyl chlorideor acetanhydride.

33.(E)-N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide

MS: Calc.: C21 H21 N3 O2 S, (379.48). Fnd.: 380.1 [M+H].

34.(E)-N-(6-Acetyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide

MS: Calc.: C19 H17 N3 O2 S, (351.43). Fnd.: 352.0 [M+H].

The following compounds 35 and 36 can be prepared according to thegeneral procedure F described below starting fromN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide(compound B1) orN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(pyridin-3-yl)-acrylamide(compound B2) and ethyl chlorothioformate.

35.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioicacid S-ethyl ester

MS: Calc.: C20 H19 N3 O2 S2 (397.52). Fnd.: 397 [M+H].

36.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioicacid S-ethyl ester

MS: Calc.: C19 H18 N4 O2 S2 (398.52). Fnd.: 398 [M+H].

The following compounds 37 and 38 can be prepared according to thegeneral procedure G described below starting fromN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide(compound B1) orN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(pyridin-3-yl)-acrylamide(compound B2) and the appropriate isocyanate oramine/carbonyldiimidazole.

37.3-Cyano-2-((E)-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethylamide

MS: Calc.: C20 H20 N4 O2 S, (380.47). Fnd.: 381 [M+H].

38.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethylamide

MS: Calc.: C19 H19 N5 O2 S, (381.46). Fnd.: 382.1 [M+H].

The following compound 39 can be prepared according to the generalprocedure A described below starting fromN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(pyridin-3-yl)-acrylamide(compound B2) and butyryl chloride.

39.(E)-N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-pyridin-3-yl-acrylamide

MS: Calc.: C20 H20 N4 O2 S, (380.47). Fnd.: 381 [M+H].

The following compounds 40 to 47 can be prepared according to thegeneral procedure E described below starting fromN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(pyridin-3-yl)-acrylamide(compound B2) and the appropriate alcohol.

40.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid isobutyl ester

MS: Calc.: C21 H22 N4 O3 S, (410.50). Fnd.: 411 [M+H].

41.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2,2-dimethyl-propyl ester

MS: Calc.: C22 H24 N4 O3 S, (424.53). Fnd.: 425 [M+H].

42.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid hexyl ester

MS: Calc.: C23 H26 N4 O3 S, (438.55). Fnd.: 439 [M+H].

43.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid butyl ester

MS: Calc.: C21 H22 N4 O3 S, (410.50). Fnd.: 411 [M+H].

44.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid methyl ester

MS: Calc.: C18 H16 N4 O3 S, (468.42). Fnd.: 369 [M+H].

45.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 3-methoxy-phenyl ester

MS: Calc.: C24 H20 N4 O4 S, (460.52). Fnd.: 461 [M+H].

46.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid phenyl ester

MS: Calc.: C23 H18 N4 O3 S, (430.49). Fnd.: 431 [M+H].

47.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid phenethyl ester

MS: Calc.: C25 H22 N4 O3 S, (458.54).

A. General Procedure for Amide Bond Formation

a) 100 mmol of an amine and 120 mmol of an appropriate acid chloride aredissolved either in a minimal amount of pyridine or toluene. In case oftoluene as solvent, 125 mmol of a base (e.g. triethylamine) is added.The reaction mixture is stirred for some time at room temperature and,if necessary, is heated for some time either by conventional ormicrowave assisted heating. Then the solvent is either removed in vacuoor the reaction mixture partitioned between water and an appropriatesolvent (e.g. ethyl acetate). In the second case, the aqueous layer isextracted several times with the organic solvent, the combined organiclayers are dried (e.g. MgSO₄) and concentrated in vacuo. Purification ofthe crude product is achieved by flash chromatography and/orrecristalization from an appropriate solvent (e.g. ethanol).

The corresponding acid chloride can be obtained in an art-known manner,such as e.g. from the free acid with the aid of a suitable chlorinationagent, e.g. oxalyl chloride, in a suitable solvent, e.g. dichloromethanewith a few drops N,N-dimethylformamide.

In some cases, the amide bond formation reaction is carried out usingone of the following methods:

b) 20 mmol of a carboxylic acid and 20 mmol of EDC are dissolved orsuspended in an appropriate solvent (e.g. dichloromethane) and 10 mmolof the amine and 0.1 mmol N,N-dimethylaminopyridine (DMAP) are added.After stirring for several hours at room temperature (If necessary, thereaction mixture is heated either by conventional heating or microwaveassisted heating.), the reaction mixture is partitioned between waterand an appropriate solvent (e.g. ethyl acetate or dichloromethane) andthe aqueous layer is extracted several times with the same organicsolvent. The combined organic layers are dried (e.g. MgSO₄) andconcentrated in vacuo. Purification of the crude product is achieved byflash chromatography and/or recristalization from an appropriate solvent(e.g. ethanol).

Starting from the appropriate starting compounds selected fromN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-methoxy-phenyl)-acrylamide,N-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamideandN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-chloro-phenyl)-acrylamidethe following compounds 48 to 51 can be prepared according to thegeneral procedure FF described later herein.

48.2-[(E)-3-(2-Chloro-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioicacid S-ethyl ester

MS: Calc.: C20 H18 Cl N3 O2 S2 (431.97). Fnd.: 432.00 [M+H].

49.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioicacid S-pentyl ester

MS: Calc.: C23 H25 N3 O2 S2 (439.60). Fnd.: 440.20 [M+H].

50.3-Cyano-2-[(E)-3-(2-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioicacid S-ethyl ester

MS: Calc.: C21 H21 N3 O3 S2 (427.55). Fnd.: 428.10 [M+H].

51.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-carbothioicacid S-(2-dimethylamino-ethyl)ester

MS: Calc.: C22 H24 N4 O2 S2 (440.59). Fnd.: 441.10 [M+H].

The following compounds 52 and 53 can be generated by treating theappropriate amine with CDI in pyridine. Purification is achieved eitherby filtration followed by washing (water) and crystallization (ethanol)or removal of solvents in vacuo and subsequent column chromatography onsilica gel, using mixtures of dichloromethane, methanol and triethylamine as eluents. If necessary, the product is recrystallized from anappropriate solvent:

52.(E)-N-[3-Cyano-6-(1-imidazol-1-yl-methanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide

MS: Calc.: C20 H16 N6 O2 S, (404.45). Fnd.: 405.10 [M+H].

53.(E)-N-[3-Cyano-6-(1-imidazol-1-yl-methanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide

MS: Calc.: C21 H17 N5 O2 S, (403.47). Fnd.: 404.00 [M+H].

AA. Alternative General Procedure for Amide Bond Formation

In a sealable test tube, the corresponding acid (1.5 mmol) is suspendedin a mixture of DMF (0.15 mmol) and dichloromethane (7.5 mL). A solutionof oxalyl chloride (3.0 mmol) in dichloromethane (7.5 mL) is then addedand the mixture stirred for 1 h at room temperature. After that, thesolvents and excess of oxalyl chloride are removed in vacuo, the residueis dissolved in toluene (7.5 mL) and added to the corresponding amine (1mmol) in a vial suitable for microwave technology. Diisopropyl ethylamine (1.5 mmol) is added, the vial capped and the mixture is heated for30 min at 150° C. using microwave technology. Purification is achievedeither by filtration followed by washing (water) and crystallization(ethanol) or removal of solvents in vacuo and subsequent columnchromatography on silica gel, using mixtures of dichloromethane,methanol and triethyl amine as eluents.

The following compounds 54 to 92, and 96 to 99 can be prepared accordingto general procedure AA mentioned above starting from2-amino-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acidtert-butyl ester or2-amino-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acidethyl ester respectively and the appropriate acrylic acid derivativeswhich are art-known or which can be prepared according to art-knownprocedures or according to general procedure H described later herein:

54.3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid tert-butyl ester

MS: Calc.: C24 H27 N3 O4 S, (453.56). Fnd.: [453.90M+H].

55.3-Cyano-2-((E)-3-furan-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid tert-butyl ester

MS: Calc.: C20 H21 N3 O4 S, (399.47). Fnd.: 798.5 [2M+H].

56.3-Cyano-2-((E)-3-furan-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid tert-butyl ester

57.2-[(E)-3-(2-Chloro-3,6-difluoro-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H16 Cl F2 N3 O3 S, (451.88). Fnd.: 452.00 [M+H].

58.3-Cyano-2-[(E)-3-(2,3-difluoro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H17 F2 N3 O3 S, (417.44). Fnd.: 418.10 [M+H].

59.2-[(E)-3-(4-Chloro-2-fluoro-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H17 Cl F N3 O3 S, (433.89). Fnd.: 434. 10 [M+H].

60.3-Cyano-2-[(E)-3-(4-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C22 H23 N3 O4 S, (425.51). Fnd.: 426.00 [M+H].

61.3-Cyano-2-[(E)-3-(3-chloro-2-fluoro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H17 Cl F N3 O3 S, (433.89). Fnd.: 434.10 [M+H].

62.3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C22 H23 N3 O4 S, (425.51). Fnd.: 426.00 [M+H].

63.3-Cyano-2-[(E)-3-(2,6-dichloro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H17 C12 N3 O3 S, (450.35). Fnd.: 450.00 [M+H].

64.2-[(E)-3-(3-Chloro-thiophen-2-yl)-allanoylamino]-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C18 H16 Cl N3 O3 S2 (421.93). Fnd.: 422.00 [M+H].

65.3-Cyano-2-[(E)-3-(2,6-difluoro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H17 F2 N3 O3 S, (417.44). Fnd.: 418.10 [M+H].

66.2-[(E)-3-(2-Bromo-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H18 Br N3 O3 S, (460.35). Fnd.: 462.00 [M+H].

67.2-[(E)-3-(2-Chloro-6-fluoro-phenyl)-allanoylamino]-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H17 Cl F N3 O3 S, (433.89). Fnd.: 434.10 [M+H].

68.3-Cyano-2-[(E)-3-(2,3,6-trifluoro-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H16 F3 N3 O3 S, (435.43). Fnd.: 436.10 [M+H].

69.2-[(E)-3-(2-Acetoxy-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C22 H21 N3 O5 S, (439.49). Fnd.: 440.00 [M+H].

70.3-Cyano-2-[(E)-3-(2-fluoro-4-methoxy-phenyl)-allanoylamino]β4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H20 F N3 O4 S, (429.47). Fnd.: 430.00 [M+H].

71.2-((E)-3-Benzo[b]thiophen-3-yl-allanoylamino)-3-cyano-[4,7-d]hydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C22 H19 N3 O3 S2 (437.54). Fnd.: 438.10 [M+H].

72.2-[(E)-3-(5-Chloro-thiophen-2-yl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C18 H16 Cl N3 O3 S2 (421.93). Fnd.: 422.10 [M+H].

73.2-((E)-3-Biphenyl-2-yl-allanoylamino)-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C26 H23 N3 O3 S, (457.56). Fnd.: 458.10 [M+H].

74.3-Cyano-2-[(E)-3-(5-methyl-furan-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-carboxylicacid ethyl ester

MS: Calc.: C19 H19 N3 O4 S, (385.44). Fnd.: 386.00 [M+H].

75.3-Cyano-2-[(E)-3-(3-methyl-thiophen-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C19 H19 N3 O3 S2 (401.51). Fnd.: 402.00 [M+H].

76.3-Cyano-2-[(E)-3-(5-methyl-thiophen-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C19 H19 N3 O3 S2 (401.51). Fnd.: 402.00 [M+H].

77.3-Cyano-2-[(E)-3-(5-ethyl-furan-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H21 N3 O4 S, (399.47). Fnd.: 400.00 [M+H].

78.2-[(E)-3-(5-Chloro-furan-2-yl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C18 H16 Cl N3 O4 S, (405.86). Fnd.: 406.00 [M+H].

79.3-Cyano-2-[(E)-3-(5-fluoro-2-methyl-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H20 F N3 O3 S, (413.47). Fnd.: 414.10 [M+H].

80.3-Cyano-2-[(E)-3-(3-fluoro-2-methyl-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H20 F N3 O3 S, (413.47). Fnd.: 414.00 [M+H].

81.3-Cyano-2-[(E)-3-(3-phenoxy-thiophen-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C24 H21 N3 O4 S2 (479.58). Fnd.: 479.90 [M+H].

82.3-Cyano-2-[(E)-3-(2-ethyl-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C22 H23 N3 O3 S, (409.51). Fnd.: 410.00 [M+H].

83.3-Cyano-2-[(E)-3-(2-cyano-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H18 N4 O3 S, (406.47). Fnd.: 407.10 [M+H].

84.2-[(E)-3-Benzofuran-2-yl-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C22 H19 N3 O4 S, (421.48). Fnd.: 422.00 [M+H].

85.3-Cyano-2-[(E)-3-(5-phenyl-thiophen-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C24 H21 N3 O3 S2 (463.58). Fnd.: 464.00 [M+H].

86.3-Cyano-2-[(E)-3-(2,3-dimethyl-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C22 H23 N3 O3 S, (409.51). Fnd.: 410.10 [M+H].

87.3-Cyano-2-[(E)-3-(2,3-dimethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C22 H23 N3 O5 S, (441.51). Fnd.: 442.00 [M+H].

88.3-Cyano-2-[(E)-3-(2-morpholin-4-yl-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C24 H26 N4 O4 S, (466.56). Fnd.: 467.20 [M+H].

89.3-Cyano-2-[(E)-3-(4-fluoro-2-methyl-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H20 F N3 O3 S, (413.47). Fnd.: 414.10 [M+H].

90.2-[(E)-3-(4-Chloro-1-methyl-1H-pyrazol-3-yl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C18 H18 Cl N5 O3 S, (419.89). Fnd.: 420.00 [M+H].

91.3-Cyano-2-[(E)-3-(5-phenyl-furan-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C24 H21 N3 O4 S, (447.52). Fnd.: 448.10 [M+H].

92.3-Cyano-2-[(E)-3-(2-morpholin-3-yl-pyridin-3-yl)-allanoylamino]-4,7-dihydro-5H-thieno-[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C23 H25 N5 O4 S, (467.55). Fnd.: 468.20 [M+H].

93.3-Cyano-2-[(E)-3-(4-hydroxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

3-Cyano-2-[(E)-3-(4-methoxy-phenyl)-allanoylamino]-4,5,6,7-tetrahydro-benzo[b]thiophene-6-carboxylicacid ethyl ester (0.16 mmol) is dissolved in 2.4 ml dichloromethane.1.22 ml BBr₃ (1M in dichloromethane) is added at −78° C. and thereaction mixture is stirred for 20 hours at room temperature. Afteraqueous workup and evaporation of the solvent, the crude product isrecristallized from ethanol.

MS: Calc.: C20 H19 N3 O4 S, (397.46). Fnd.: 398.00 [M+H].

The following compounds 94 and 95 can be prepared analogously to thepreparation of Example 93.

94.3-Cyano-2-[(E)-3-(3-hydroxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H19 N3 O4 S, (397.46). Fnd.: 398.10 [M+H].

95.3-Cyano-2-[(E)-3-(2-hydroxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C20 H19 N3 O4 S, (397.46). Fnd.: 398.00 [M+H].

96.3-Cyano-2-[(E)-3-(2-ethoxy-3-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C23 H25 N3 O5 S, (455.54). Fnd.: 456.00 [M+H].

97.3-Cyano-2-[(E)-3-(1-methyl-1H-pyrrol-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C19 H20 N4 O3 S, (384.46). Fnd.: 385.10 [M+H].

98.3-Cyano-2-[(E)-3-(2-isopropoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C23 H25 N3 O4 S, (439.54). Fnd.: 440.00 [M+H].

99.3-Cyano-2-[(E)-3-(2-propoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C23 H25 N3 O4 S, (439.54). Fnd.: 439.90 [M+H].

The following compounds 100 to 104, 106, and 108 to 111 can be preparedaccording to general procedure M mentioned above starting from2-amino-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acidethyl ester and the appropriate acrylic acid derivatives which can beprepared according to general procedure H described later herein.

100.3-Cyano-2-((E)-3-pyridin-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C19 H18 N4 O3 S, (382.44). Fnd.: 383.10 [M+H].

101.3-Cyano-2-((E)-3-pyridin-4-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C19 H18 N4 O3 S, (382.44). Fnd.: 383.10 [M+H].

102.3-Cyano-2-[(E)-3-(2,5-dimethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C22 H23 N3 O5 S, (441.51). Fnd.: 441.90 [M+H].

103.3-Cyano-2-((E)-3-1-H-pyrrol-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethylester

MS: Calc.: C18 H18 N4 O3 S, (370.43). Fnd.: 371.10 [M+H].

104.3-Cyano-2-[(E)-3-(2-phenoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C26 H23 N3 O4 S, (473.55). Fnd.: 473.90 [M+H].

105.3-Cyano-2-{(E)-3-[2-(2-hydroxy-ethoxy)-phenyl]-allanoylamino}-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

This compound is prepared in analogy to(E)-N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide.

MS: Calc.: C22 H23 N3 O5 S, (441.51). Fnd.: 442.00 [M+H].

106.5-Cyano-6-[(E)-3-(2,6-dimethoxy-phenyl)-allanoylamino]-1,3,4,7-tetrahydro-[2]pyridine-2-carboxylicacid ethyl ester

MS: Calc.: C22 H23 N3 O5 S, (441.51). Fnd.: 442.00 [M+H].

107.3-Cyano-2-{(E)-3-[3-(2-hydroxy-ethoxy)-phenyl]-allanoyl-amino}-4,7-dihydro-5H-thieno[2,3-c]-pyridine-6-carboxylicacid ethyl ester

This compound is prepared in analogy to(E)-N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide.

MS: Calc.: C22 H23 N3 O5 S, (441.51). Fnd.: 442.10 [M+H].

108.3-Cyano-2-[(E)-3-(2,6-dimethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C22 H23 N3 O5 S, (441.51). Fnd.: 442.00 [M+H].

109.2-[(E)-3-(5-Bromo-2-ethoxy-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C22 H22 Br N3 O4 S, (504.41). Fnd.: 505.10 [M+H].

110.2-[(E)-3-(5-Bromo-2-methoxy-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H20 Br N3 O4 S, (490.38). Fnd.: 489.9 [M−H].

111.2-((E)-3-Benzo[1,3]dioxol-4-yl-allanoylamino)-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H19 N3 O5 S, (425.47). Fnd.: 426.10 [M+H].

The following compounds 112 to 127, 129, 130, 132 to 134, 132 to 134,135 to 164, and 166 to 168 can be prepared starting from the appropriatestarting compound selected fromN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide,N-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-methoxy-phenyl)-acrylamide,N-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-chloro-phenyl)-acrylamideandN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(pyridin-3-yl)-acrylamideaccording to general procedure EE as described later herein:

112.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-morpholin-4-yl-ethyl ester

MS: Calc.: C24 H26 N4 O4 S, (466.56). Fnd.: 467.20 [M+H].

113.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-dimethylamino-ethyl ester

MS: Calc.: C22 H24 N4 O3 S, (424.53). Fnd.: 425.10 [M+H].

114.3-Cyano-2-((E1-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-pyrrolidin-1-yl-ethyl ester

MS: Calc.: C24 H26 N4 O3 S, (450.56). Fnd.: 451.20 [M+H].

115.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 3-dimethylamino-propyl ester

MS: Calc.: C23 H26 N4 O3 S, (438.55). Fnd.: 439.20 [M+H].

116.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-pyridin-2-yl-ethyl ester

MS: Calc.: C25 H22 N4 O3 S, (458.54). Fnd.: 459.10 [M+H].

117.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 3-pyridin-4-yl-propyl ester

MS: Calc.: C26 H24 N4 O3 S, (472.57). Fnd.: 473.20 [M+H].

118.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-methoxy-ethyl ester

MS: Calc.: C21 H21 N3 O4 S, (411.48). Fnd.: 412.00 [M+H].

119.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 3-piperidin-1-yl-propyl ester

MS: Calc.: C26 H30 N4 O3 S, (478.62). Fnd.: 479.20 [M+H].

120.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 3-morpholin-4-yl-propyl ester

MS: Calc.: C25 H28 N4 O4 S, (480.59). Fnd.: 481.20 [M+H].

121.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 3-(4-methyl-piperazin-1-yl)-propyl ester

MS: Calc.: C26 H31 N5 O3 S, (493.63). Fnd.: 494.30 [M+H].

122.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester

MS: Calc.: C24 H22 N6 O5 S, (506.54). Fnd.: 507.10 [M+H].

123.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-(4-nitro-phenoxy)-ethyl ester

MS: Calc.: C26 H22 N4 O6 S, (518.55). Fnd.: 519.10 [M+H].

124.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-carboxylicacid 3-pyridin-2-yl-propyl ester

MS: Calc.: C26 H24 N4 O3 S, (472.57). Fnd.: 473.10 [M+H].

125.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 3-pyridin-3-yl-propyl ester

MS: Calc.: C26 H24 N4 O3 S, (472.57). Fnd.: 473.20 [M+H].

126.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-pyridin-4-yl-ethyl ester

MS: Calc.: C25 H22 N4 O3 S, (458.54). Fnd.: 459.10 [M+H].

127.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester

MS: Calc.: C24 H25 N3 O5 S, (467.55). Fnd.: 468.10 [M+H].

128.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2,3-dihydroxy-propyl ester

This compound is prepared in analogy to3-cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2,3-dihydroxy-propyl ester.

MS: Calc.: C21 H21 N3 O5 S, (427.48). Fnd.: 428.10 [M+H].

129.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-(2-methoxy-ethoxy)-ethyl ester

MS: Calc.: C23 H25 N3 O5 S, (455.54). Fnd.: 456.00 [M+H].

130.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-piperidin-1-yl-ethyl ester

MS: Calc.: C25 H28 N4 O3 S, (464.59). Fnd.: 465.20 [M+H].

131.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid carboxymethyl ester

This compound is prepared by standard saponification of the esterfunction of3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid methoxycarbonylmethyl ester.

MS: Calc.: C20 H17 N3 O5 S, (411.44). Fnd.: 412.00 [M+H].

132.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-(4-methyl-piperazin-1-yl)-ethyl ester

MS: Calc.: C25 H29 N5 O3 S, (479.61). Fnd.: 480.20 [M+H].

133.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid methoxycarbonylmethyl ester

MS: Calc.: C21 H19 N3 O5 S, (425.47). Fnd.: 426.10 [M+H].

134.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-acetylamino-ethyl ester

MS: Calc.: C22 H22 N4 O4 S, (438.51). Fnd.: 439.10 [M+H].

135.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-hydroxy-ethyl ester

This compound is prepared according to(E)-N-[3-cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide.

MS: Calc.: C20 H19 N3 O4 S, (397.46). Fnd.: 398.10 [M+H].

136.3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-imidazol-1-yl-ethyl ester

MS: Calc.: C23 H21 N5 O3 S, (447.52). Fnd.: 448.20 [M+H].

137.3-Cyano-2-[(E)-3-(2-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-methoxy-ethyl ester

MS: Calc.: C22 H23 N3 O5 S, (441.51). Fnd.: 442.10 [M+H].

138.3-Cyano-2-[(E)-3-(2-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid pyridin-2-ylmethyl ester

MS: Calc.: C25 H22 N4 O4 S, (474.54). Fnd.: 475.10 [M+H].

139.3-Cyano-2-[(E)-3-(2-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-pyridin-2-yl-ethyl ester

MS: Calc.: C26 H24 N4 O4 S, (488.57). Fnd.: 489.10 [M+H].

140.3-Cyano-2-[(E)-3-(2-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid pyridin-3-ylmethyl ester

MS: Calc.: C25 H22 N4 O4 S, (474.54). Fnd.: 475.20 [M+H].

141.3-Cyano-2-[(E)-3-(2-methoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid pyridin-4-ylmethyl ester

MS: Calc.: C25 H22 N4 O4 S, (474.54). Fnd.: 475.20 [M+H].

142.2-[(E)-3-(2-Chloro-phenyl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-methoxy-ethyl ester

MS: Calc.: C21 H20 Cl N3 O4 S, (445.93). Fnd.: 446.00 [M+H].

143.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 4-methoxy-phenyl ester

MS: Calc.: C24 H20 N4 O4 S, (460.52). Fnd.: 461.20 [M+H].

144.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid benzyl ester

MS: Calc.: C24 H20 N4 O3 S, (444.52). Fnd.: 445.10 [M+H].

145.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid propyl ester

MS: Calc.: C20 H20 N4 O3 S, (396.47). Fnd.: 397.10 [M+H].

146.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-(4-methoxy-phenyl)-ethyl ester

MS: Calc.: C26 H24 N4 O4 S, (488.57). Fnd.: 489.10 [M+H].

147.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 3-methoxy-benzyl ester

MS: Calc.: C25 H22 N4 O4 S, (474.54). Fnd.: 475.10 [M+H].

148.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 3-phenyl-propyl ester

MS: Calc.: C26 H24 N4 O3 S, (472.57). Fnd.: 473.20 [M+H].

149.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid pyridin-2-ylmethyl ester

MS: Calc.: C23 H19 N5 O3 S, (445.50). Fnd.: 446.20 [M+H].

150.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid pyridin-3-ylmethyl ester

MS: Calc.: C23 H19 N5 O3 S, (445.50). Fnd.: 446.20 [M+H].

151.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 4-methoxycarbonyl-phenyl ester

MS: Calc.: C25 H20 N4 O5 S, (488.53). Fnd.: 489.20 [M+H].

152.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-(3-methoxy-phenyl)-ethyl ester

MS: Calc.: C26 H24 N4 O4 S, (488.57). Fnd.: 489.20 [M+H].

153.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-(2-methoxy-phenyl)-ethyl ester

MS: Calc.: C26 H24 N4 O4 S, (488.57). Fnd.: 489.10 [M+H].

154.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid pyridin-2-yl ester

MS: Calc.: C22 H17 N5 O3 S, (431.48). Fnd.: 432.00 [M+H].

155.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid methyl ester

MS: Calc.: C18 H16 N4 O3 S, (368.42). Fnd.: 469.10 [M+H].

156. 3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acid2-morpholin-4-yl-ethyl ester

MS: Calc.: C23 H25 N5 O4 S, (467.55). Fnd.: 468.10 [M+H].

157.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 3-pyridin-3-yl-propyl ester

MS: Calc.: C25 H23 N5 O3 S, (473.56). Fnd.: 474.20 [M+H].

158.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-pyridin-2-ylethyl ester

MS: Calc.: C24 H21 N5 O3 S, (459.53). Fnd.: 460.20 [M+H].

159.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-pyridin-3-yl-ethyl ester

MS: Calc.: C24 H21 N5 O3 S, (459.53). Fnd.: 460.20 [M+H].

160.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-carboxylicacid pyridin-4-ylmethyl ester

MS: Calc.: C23 H19 N5 O3 S, (445.50). Fnd.: 446.20 [M+H].

161.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethoxycarbonylmethyl ester

MS: Calc.: C21 H20 N4 O S, (440.48). Fnd.: 441.10 [M+H].

162.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-methoxycarbonyl-ethyl ester

MS: Calc.: C21 H20 N4 O5 S, (440.48). Fnd.: 441.10 [M+H].

163.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-carboxylicacid 3-dimethylamino-propyl ester

MS: Calc.: C22 H25 N5 O3 S, (439.54). Fnd.: 440.20 [M+H].

164.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester

MS: Calc.: C23 H24 N4 O5 S, (468.54). Fnd.: 469.00 [M+H].

165.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2,3-dihydroxy-propyl ester

0.26 mmol of3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester are dissolved in 10 mlAcCN/H2O (2/1) and 0.1 eq PTSA is added. After stirring over night, sometriethylamine is added and the solvent removed. Recrystallization fromethanol gives the desired product in 80% yield.

MS: Calc.: C20 H20 N4 O5 S, (428.47). Fnd.: 429.00 [M+H].

166.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-benzyloxy-ethyl ester

MS: Calc.: C26 H24 N4 O4 S, (488.57). Fnd.: 489.20 [M+H].

167.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-methoxy-ethyl ester

MS: Calc.: C20 H20 N4 O4 S, (412.47). Fnd.: 413.10 [M+H].

168.3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid cyclohexyl ester

MS: Calc.: C23 H24 N4 O3 S, (436.54). Fnd.: 437.10 [M+H].

AAA. Further Alternative General Procedure for the Formation of AmideBonds

a) Starting from the Trifluoroacetate Salt:

To a solution of the appropriate acid (1.5 mmol) in dichloromethane (5ml), carbonyldiimidazole (CDI, 1.78 mmol) is added. The reaction vesselis equipped with a bubbler, the mixture is stirred until the gasevolution is completed (30 min, approximately). Then, a mixture of thesuspension of the appropriate starting trifluoroacetate salt indichloromethane (10 ml) and triethylamine (0.2 g, 2 mmole) is added tothe reaction mixture. Stirring is continued for 18 to 24 hours at roomtemperature, the reaction is monitored by TLC.

Work up A: if the reaction mixture is a solution, it is extracted bythree portions of 5% sodium hydrogencarbonate (10 ml each) and once bywater (10 ml), the organic layer is evaporated and the residue subjectedto purification.

Work up B: if the reaction mixture is a suspension, the solid product isfiltered off. If the amount of this solid product is not sufficient, themother liquor is further worked up as procedure A.

Purification: The majority of the products can be recrystallized fromacetonitrile, in some cases by simple trituration of the organic residuewith acetonitrile. After filtration, the crystals are washed withdiethyl ether.

b) Starting from the Free Amine Using EDCL

A mixture of the appropriate starting base (1 mmol), the appropriateacid (1.5 mmol), ethyl-dimethylaminopropylcarbodiimide (EDCl, 0.29 g,1.5 mmol), 4-dimethylaminopyridine (DMAP, 0.25 g, 0.2 mmol) andwater-free dichloromethane (10 ml) are stirred at room temperature for18 to 24 hours. The reaction mixture is monitored by TLC. The reactionmixture is worked up as in the reactions carried out with CDI.

c) Using Acid Chlorides

To a suspension of the appropriate starting trifluoroacetate salt (1mmol) in dichloromethane (10 ml) triethylamine (0.4 g, 4 mmol) is added.The formed solution is added to a solution of the appropriate acidchloride (1.2 mmol) in dichloromethane (10 ml) dropwise at 0° C. withstirring and, then, stirring is continued for 24 h at room temperature.The mixture is evaporated and the residue dissolved in dichloromethane.This solution is extracted twice by water (15 ml) and once by saturatedsodium chloride solution (15 ml). Purification is carried out asdescribed in procedures a) and b).

The following compounds 169 to 186, 188 to 191, 193 to 198, 200 to 203,and 205 to 229 can be prepared starting from the appropriate startingcompound selected fromN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide,N-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-methoxy-phenyl)-acrylamide,N-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-ethoxy-phenyl)-acrylamide,N-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-chloro-phenyl)-acrylamide,N-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(furan-2-yl)-acrylamideandN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(pyridin-3-yl)-acrylamideaccording to general procedure AAA mentioned above.

169.(E)-N-(6-Acetyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide

MS: Calc.: C19 H17 N3 O2 S, (351.43). Fnd.: 352.00 [M+H].

170.(E)-N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide

MS: Calc.: C21 H21 N3 O2 S, (379.48). Fnd.: 380.10 [M+H].

171.(E)-N-[3-Cyano-6-(3-1H-indol-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide

MS: Calc.: C28 H24 N4 O2 S, (480.59). Fnd.: 481.10 [M+H].

172.(E)-N-[3-Cyano-6-(4-1H-indol-3-yl-butanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide

MS: Calc.: C29 H26 N4 O2 S, (494.62). Fnd.: 495.20 [M+H].

173.4-[3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-4-oxo-butyricacid methyl ester

MS: Calc.: C22 H21 N3 O4 S, (423.49). Fnd.: 424.00 [M+H].

174.(E)-N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide

MS: Calc.: C24 H20 N4 O2 S, (428.52). Fnd.: 429.20 [M+H].

175.(E)-N-{3-Cyano-6-[2-(2-methoxy-ethoxy)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-acrylamide

MS: Calc.: C22 H23 N3 O4 S, (425.51). Fnd.: 426.10 [M+H].

176.3-[3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-3-oxo-propionicacid ethyl ester

MS: Calc.: C22 H21 N3 O4 S, (423.49). Fnd.: 424.10 [M+H].

177.(E)-N-[3-Cyano-6-(3-methoxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide

MS: Calc.: C21 H21 N3 O3 S, (395.48). Fnd.: 396.10 [M+H].

178.4-[3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-N,N-dimethyl-4-oxo-butyramide

MS: Calc.: C23 H24 N4 O3 S, (436.54). Fnd.: 437.00 [M+H].

179.(E)-N-[3-Cyano-6-(3-ureido-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide

MS: Calc.: C21 H21 N5 O3 S, (423.50). Fnd.: 424.10 [M+H].

180.(E)-N-[3-Cyano-6-(3-guanidino-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide

MS: Calc.: C21 H22 N6 O2 S, (422.51). Fnd.: 423.10 [M+H].

181.(E)-N-[3-Cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide

MS: Calc.: C20 H19 N3 O3 S, (381.46). Fnd.: 382.10 [M+H].

182.(E)-N-[3-Cyano-6-(2-1H-indol-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide

MS: Calc.: C27 H22 N4 O2 S, (466.57). Fnd.: 467.10 [M+H].

183.(E)-N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide

MS: Calc.: C24 H20 N4 O2 S, (428.52). Fnd.: 429.20 [M+H].

184.(E)-N-{3-Cyano-6-[4-(4-methanesulfonyl-phenyl)-4-oxo-butanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-phenyl-acrylamide

MS: Calc.: C28 H25 N3 O5 S2 (547.66). Fnd.: 548.00 [M+H].

185.(E)-N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide

MS: Calc.: C25 H22 N4 O2 S, (442.54). Fnd.: 443.20 [M+H].

186.5-[3-Cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-5-oxo-pentanoicacid methyl ester

MS: Calc.: C23 H23 N3 O4 S, (437.52). Fnd.: 438.00 [M+H].

187.(E)-N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide

1 mmol of acetic acid2-[3-cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-2-oxo-ethylester are stirred in 5 ml methanol and 1 ml 45% aqueous NaOH until thereaction is completed. Purification according to the previouspreparation affords the desired compound.

MS: Calc.: C19 H17 N3 O3 S, (367.43). Fnd.: 368.00 [M+H].

188.(E)-N-[3-Cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide

MS: Calc.: C22 H19 N5 O2 S, (417.49). Fnd.: 418.20 [M+H].

189. Acetic acid2-[3-cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-2-oxo-ethylester

190.(E)-N-[3-Cyano-6-(4-imidazol-1-yl-butanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide

MS: Calc.: C24 H23 N5 O2 S, (445.55). Fnd.: 446.10 [M+H].

191. Acetic acid4-[3-cyano-2-((E)-3-phenyl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-4-oxo-butylester

MS: Calc.: C23 H23 N3 O4 S, (437.52). Fnd.: 438.00 [M+H].

192.(E)-N-[3-Cyano-6-(4-hydroxy-butanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide

This compound is prepared in analogy to(E)-N-[3-cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-phenyl-acrylamide.

MS: Calc.: C21 H21 N3 O3 S, (395.48). Fnd.: 396.00 [M+H].

193.(E)-N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide

MS: Calc.: C24 H21 N5 O2 S, (443.53). Fnd.: 444.20 [M+H].

194.(E)-N-[3-Cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide

MS: Calc.: C19 H18 N4 O3 S, (382.44). Fnd.: 383.10 [M+H].

195.(E)-N-[3-Cyano-6-(3-methoxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide

MS: Calc.: C20 H20 N4 O3 S, (396.47). Fnd.: 397.10 [M+H].

196.(E)-N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide

MS: Calc.: C23 H19 N5 O2 S, (429.50). Fnd.: 430.10 [M+H].

197.(E)-N-[3-Cyano-6-(3-[1,2,4]triazol-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide

MS: Calc.: C21 H19 N7 O2 S, (433.50). Fnd.: 434.10 [M+H].

198.(E)-N-[3-Cyano-6-(3-thiazol-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide

MS: Calc.: C22 H19 N5 O2 S2 (449.56). Fnd.: 450.10 [M+H].

199.4-[3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-4-oxo-butyricacid

This compound is prepared by standard saponification of the esterfunction of the appropriate methyl ester.

MS: Calc.: C20 H18 N4 O4 S, (410.45). Fnd.: 411.10 [M+H].

200.(E)-N-{3-Cyano-6-[2-(2-methoxy-ethoxy)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-pyridin-3-yl-acrylamide

MS: Calc.: C21 H22 N4 O4 S, (426.50). Fnd.: 427.10 [M+H].

201.{3-[3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-3-oxo-propyl}-carbamicacid tert-butyl ester

MS: Calc.: C24 H27 N5 O4 S, (481.58). Fnd.: 481.90 [M+H].

202.{4-[3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-4-oxo-butyl}-carbamicacid tert-butyl ester

MS: Calc.: C25 H29 N5 O4 S, (495.60). Fnd.: 495.90 [M+H].

203.{2-[3-Cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-2-oxoethyl}-carbamicacid tert-butyl ester

MS: Calc.: C23 H25 N5 O4 S, (467.55). Fnd.: 467.90 [M+H].

204.(E)-N-[6-(4-Amino-butanoyl)-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide

This compound is prepared by standard Boc-deprotection starting from{4-[3-cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-4-oxo-butyl}-carbamicacid tert-butyl ester

MS: Calc.: C20 H21 N5 O2 S, (395.49). Fnd.: 396.00 [M+H].

205.(E)-N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-pyridin-3-yl-acrylamide

MS: Calc.: C23 H19 N5 O2 S, (429.50). Fnd.: 430.20 [M+H].

206.(E)-N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-acrylamide

MS: Calc.: C26 H24 N4 O3 S, (472.57). Fnd.: 473.20 [M+H].

207.(E)-N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-acrylamide

MS: Calc.: C25 H22 N4 O3 S, (458.54). Fnd.: 459.10 [M+H].

208.(E)-N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-acrylamide

MS: Calc.: C25 H22 N4 O3 S, (458.54). Fnd.: 459.20 [M+H].

209.(E)-N-{3-Cyano-6-[2-(2-methoxy-ethoxy)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-phenyl)-acrylamide

MS: Calc.: C23 H25 N3 O5 S, (455.54). Fnd.: 456.10 [M+H].

210.(E)-N-[3-Cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-acrylamide

MS: Calc.: C21 H21 N3 O4 S, (411.48). Fnd.: 412.10 [M+H].

211.(E)-N-[3-Cyano-6-(3-methoxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-acrylamide

MS: Calc.: C22 H23 N3 O4 S, (425.51). Fnd.: 426.10 [M+H].

212.(E)-3-(2-Chloro-phenyl)-N-[3-cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-acrylamide

MS: Calc.: C24 H19 Cl N4 O2 S, (462.96). Fnd.: 463.30 [M+H].

213.(E)-3-(2-Chloro-phenyl)-N-[3-cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-acrylamide

MS: Calc.: C24 H19 Cl N4 O2 S, (462.96). Fnd.: 463.10 [M+H].

214.(E)-3-(2-Chloro-phenyl)-N-[3-cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-acrylamide

MS: Calc.: C24 H19 Cl N4 O2 S, (462.96). Fnd.: 463.20 [M+H].

215.(E)-3-(2-Chloro-phenyl)-N-[3-cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-acrylamide

MS: Calc.: C25 H21 Cl N4 O2 S, (476.99). Fnd.: 477.20 [M+H].

216.(E)-N-[3-Cyano-6-(3-methoxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide

MS: Calc.: C23 H25 N3 O4 S, (439.54). Fnd.: 440.2 [M+H].

217.(E)-N-{3-Cyano-6-[2-(2-methoxy-ethoxy)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-acrylamide

MS: Calc.: C24 H27 N3 O5 S, (469.56). Fnd.: 470.2 [M+H].

218.(E)-N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide

MS: Calc.: C26 H24 N4 O3 S, (472.57). Fnd.: 473.2 [M+H].

219.(E)-N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide

MS: Calc.: C26 H24 N4 O3 S, (472.57). Fnd.: 473.3 [M+H].

220.(E)-N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide

MS: Calc.: C27 H26 N4 O3 S, (486.6). Fnd.: 487.3 [M+H].

221.(E)-N-[3-Cyano-6-(3-phenyl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide

MS: Calc.: C28 H27 N3 O3 S, (485.61). Fnd.: 486.2 [M+H].

222.(E)-N-[3-Cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide

MS: Calc.: C27 H26 N4 O3 S, (486.6). Fnd.: 487.3 [M+H].

223.(E)-N-[3-Cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide

MS: Calc.: C22 H23 N3 O4 S, (425.51). Fnd.: 426.1 [M+H].

224.(E)-N-[3-Cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-acrylamide

MS: Calc.: C25 H25 N5 O3 S, (475.57). Fnd.: 476.3 [M+H].

225.(E)-N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-ethoxy-phenyl)-acrylamide

MS: Calc.: C23 H25 N3 O3 S, (423.54). Fnd.: 424.2 [M+H].

226.(E)-N-{3-Cyano-6-[2-(2-methoxy-ethoxy)ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-furan-2-yl-acrylamide

MS: Calc.: C20 H21 N3 O5 S, (415.47). Fnd.: 416.1 [M+H].

227.(E)-N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-furan-2-yl-acrylamide

MS: Calc.: C22 H18 N4 O3 S, (418.48). Fnd.: 419.1 [M+H].

228.(E)-N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-furan-2-yl-acrylamide

MS: Calc.: C22 H18 N4 O3 S, (418.48). Fnd.: 419.2 [M+H].

229.(E)-N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-furan-2-yl-acrylamide

MS: Calc.: C23 H20 N4 O3 S, (432.5). Fnd.: 433.3 [M+H].

The following compounds 230 to 234 can be prepared according to generalprocedure AA mentioned above starting from2-amino-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylic acidethyl ester and the Appropriate acrylic acid derivatives which areart-known or which can be prepared according to art-known procedures oraccording to general procedure H described later herein.

230.3-Cyano-2-[(E)-3-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H17 F2 N3 O5 S, (461.45). Fnd.: 462 [M+H].

231. 3-Cyano-2{(E),3-[2-(1,1-difluoro-methoxy)-phenyl]-allanoylamino}-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H19 F2 N3 O4 S, (447.46). Fnd.: 448.1 [M+H].

232.2-[(E)-3-(4-Bromo-benzo[1,3]dioxol-5-yl)-allanoylamino]-3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H18 Br N3 O5 S, (504.36). Fnd.: 504.0+506.0 [M+H].

233.3-Cyano-2-[(E)-3-(2-trifluoromethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C21 H18 F3 N3 O4 S, (465.45). Fnd.: 466.2 [M+H].

234.3-Cyano-2-((E)-3-2,3-dihydro-benzofuran-7-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethyl ester

MS: Calc.: C22 H21 N3 O4 S, (423.49). Fnd.: 424.1 [M+H].

The following compounds 235 to 243 can be prepared starting from theappropriate starting compound selected fromN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-ethoxy-phenyl)-acrylamideandN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(furan-2-yl)-acrylamideaccording to general procedure EE as described later herein.

235.3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-methoxy-ethyl ester

MS: Calc.: C23 H25 N3 O5 S, (455.54). Fnd.: 456.1 [M+H].

236.3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-carboxylicacid pyridin-2-ylmethyl ester

MS: Calc.: C26 H24 N4 O4 S, (488.57). Fnd.: 489.1 [M+H].

237.3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid pyridin-3-ylmethyl ester

MS: Calc.: C26 H24 N4 O4 S, (488.57). Fnd.: 489.3 [M+H].

238.3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid pyridin-4-ylmethyl ester

MS: Calc.: C26 H24 N4 O4 S, (488.57). Fnd.: 489.3 [M+H].

239.3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-pyridin-2-yl-ethyl ester

MS: Calc.: C27 H26 N4 O4 S, (502.6). Fnd.: 503.3 [M+H].

240.3-Cyano-2-((E)-3-furan-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-methoxy-ethyl ester

MS: Calc.: C19 H19 N3 O5 S, (401.44). Fnd.: 402.1 [M+H].

241.3-Cyano-2-((E)-3-furan-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid pyridin-2-ylmethyl ester

MS: Calc.: C22 H18 N4 O4 S, (434.48). Fnd.: 435.2 [M+H].

242.3-Cyano-2-((E)-3-furan-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid pyridin-3-ylmethyl ester

MS: Calc.: C22 H18 N4 O4 S, (434.48). Fnd.: 435.3 [M+H].

243.3-Cyano-2-((E)-3-furan-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid 2-pyridin-2-yl-ethyl ester

MS: Calc.: C23 H20 N4 O4 S, (448.5). Fnd.: 449.2 [M+H].

244.3-Cyano-2-((E)-3-furan-2-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid pyridin-4-yl-methyl ester

The title compound may be obtained analogously as described for Example243.

The following compound 245 can be prepared according to generalprocedure G described below starting fromN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-ethoxy-phenyl)-acrylamideand the appropriate isocyanate or amine/carbonyldiimidazole.

245.3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid ethylamide

MS: Calc.: C22 H24 N4 O3 S, (424.53). Fnd.: 425.1 [M+H].

The following compounds 246 to 251 may be prepared according to generalprocedure FF described later herein starting fromN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-ethoxy-phenyl)-acrylamideorN-(3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(furan-2-yl)-acrylamiderespectively.

-   246.    3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-carbothioic    acid S-ethyl ester-   247.    3-Cyano-2-[(E)-3-(furan-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioic    acid S-ethyl ester-   248.    3-Cyano-2-[(E)-3-(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-carbothioic    acid S-(2-pyridin-4-yl-ethyl)ester-   249.    3-Cyano-2-[(E)-3-(furan-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioic    acid S-(2-pyridin-4-yl-ethyl)ester-   250. 3-Cyano-2-[(E)    —(2-ethoxy-phenyl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-carbothioic    acid S-(2-pyridin-2-yl-ethyl)ester-   251.    3-Cyano-2-[(E)-3-furan-2-yl)-allanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbothioic    acid S-(2-pyridin-2-yl-ethyl)ester    Starting Materials:

A1 2-Amino-3-cyano-4,7-dihydro-thieno[2,3-c]pyridine-6(5H)-carboxylicacid ethyl ester

Prepared according to general procedure B described below starting fromN-carbethoxy-4-piperidone.

MS: Calc.: C₁₁H₁₃N₃O₂S, (251.31). Fnd.: 252.0 [M+H].

B. General Procedure for Condensed 2-Amino-Thiophene-3-CarbonitrileDerivatives

500 mmol of cyclic ketone and 500 mmol of malononitrile are dissolved ina minimal volume of ethanol and 500 mmol elemental sulfur are added.After addition of 500 mmol diethyl amine, the reaction mixture is heatedto 60-70° C. for some minutes and then stirred at room temperature forseveral hours. The reaction mixture is poured on ice/water and theprecipitate filtered off. In case there is no or only some precipitateformed, the aqueous layer is extracted several times withdichloromethane or another appropriate organic solvent, the combinedorganic layers are dried (e.g. MgSO₄) and concentrated in vacuo.Purification of the crude product is achieved by flash chromatographyand/or recrystallization from an appropriate solvent (e.g. ethanol).

A2. 2-Amino-3-cyano-4,7-dihydro-thieno[2,3-c]pyridine-6(5H)-carboxylicacid 1,1-dimethylethyl ester

Prepared according to general procedure B starting fromBoc-4-piperidone.

MS: Calc.: C₁₃H₁₇N₃O₂S, (279.36). Fnd.: 280.0 [M+H].

B1.N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide

Prepared according to general procedure C described below starting fromN-(6-tertbutoxycarbonyl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-phenyl-acrylamide(compound 2).

MS: Calc.: C₁₇H₁₅N₃OS, (309.39). Fnd.: 310.0 [M+H].

B2.N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(pyridin-3-yl)acrylamide

The title compound can be prepared according to general procedure Cdescribed below starting from3-cyano-2-((E)-3-pyridin-3-yl-allanoylamino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carboxylicacid tert-butyl ester (compound 32).

Using similar procedures as described for the compounds B1 or B2, butwith suitable choice of starting materials, the following compounds maybe prepared:

-   B3.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-methoxyphenyl)-acrylamide-   B4.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-ethoxyphenyl)-acrylamide-   B5.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-chlorophenyl)-acrylamide-   B6.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-methylphenyl)-acrylamide-   B7.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-methoxy-3-methyl-phenyl)-acrylamide-   B8.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-ethoxy-3-methyl-phenyl)-acrylamide-   B9.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-methoxy-5-methyl-phenyl)-acrylamide-   B10.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-ethoxy-5-methyl-phenyl)-acrylamide-   B11.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-ethoxy-3-methoxy-phenyl)-acrylamide-   B12.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-ethoxy-5-methoxy-phenyl)-acrylamide-   B13.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2,3-dimethoxy-phenyl)-acrylamide-   B14.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2,5-dimethoxy-phenyl)-acrylamide-   B15.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-methyl-3-methoxy-phenyl)-acrylamide-   B16.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-methyl-5-methoxy-phenyl)-acrylamide-   B17.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2,3-dimethyl-phenyl)-acrylamide-   B18.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2,5-dimethyl-phenyl)-acrylamide-   B19.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-chloro-3-methoxy-phenyl)-acrylamide-   B20.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-chloro-5-methoxy-phenyl)-acrylamide-   B21.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-chloro-3-methyl-phenyl)-acrylamide-   B22.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-chloro-5-methyl-phenyl)-acrylamide-   B23.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(furan-2-yl)-acrylamide-   B24.    N-(3-Cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(furan-3-yl)-acrylamide

C. General Procedure for Removal of Boc Protecting Groups

The Boc protected compound is dissolved indichloromethane/trifluoroacetic acid (TFA) (2/3) and stirred for severalhours at room temperature. After evaporation of the solvent andrecristalization from an appropriate solvent (e.g. ethanol), the desiredproduct is obtained as TFA salt. The TFA salt may be converted into thefree base in a manner customary per se to the skilled person.

D. General Procedure for Sulfonamide Bond Formation

100 mmol of the amine and 150 mmol of the sulfonyl chloride aredissolved in pyridine and stirred for some time at room temperature and,if necessary, is heated for some time

either by conventional or microwave assisted heating. Then the solventis

either removed in vacuo or the reaction mixture is partitioned betweenwater and an appropriate solvent (e.g. ethyl acetate). In the secondcase, the aqueous layer is extracted several times with the organicsolvent, the combined organic layers are dried (e.g. MgSO₄) andconcentrated in vacuo. Purification of the crude product is achieved byflash chromatography and/or recristalization from an appropriate solvent(e.g. ethanol).

E. General Procedure for Carbamate Formation

100 mmol pyridine and 65 mmol triphosgene are dissolved indichloromethane. 65 mmol of the alcohol are added at 0° C. and thereaction is stirred at room temperature for 3 hours. This solution isadded to 200 mmol of the amine in dichloromethane at −78° C. and thereaction mixture is allowed to warm to room temperature and stirred forsome time. Then the solvent is

either removed in vacuo or the reaction mixture is partitioned betweenwater and an appropriate solvent (e.g. ethyl acetate). In the secondcase, the aqueous layer is extracted several times with the organicsolvent, the combined organic layers are dried (e.g. MgSO₄) andconcentrated in vacuo. Purification of the crude product is achieved byflash chromatography and/or recristalization from an appropriate solvent(e.g. ethanol).

EE. Alternative General Procedure for the Preparation of Carbamates

A) Preparation of the imidazole 1-carboxylic ester reagents:

A solution of the appropriate alcohol (10 mmol),1,1′-carbonyldiimidazole (10 mmol) in dichloromethane (20 ml) is stirredat room temperature for 2 to 3 h while the reaction is monitored by TLC.Then the reaction mixture is extracted by three portions of 10% sodiumhydrogencarbonate solution and once by water. The organic layer is driedover sodium sulfate and evaporated to yield a pale yellow oil orcolorless solid.

B) Synthesis of carbamates:

To a suspension of the appropriate base (1 mmol) and reagent (1 mmole)in abs. dichloromethane (15 ml), DBU (1.15 mmol) is added and themixture is stirred for 2 to 7 days, the reaction is monitored by TLC(silica, dichloromethane-methanol 10:1 mixture as an eluent). Thereaction mixture is extracted twice by 10% sodium hydrogencarbonatesolution, once by water, and the organic layer is dried over sodiumsulfate. After evaporation the residue is treated with diethyl ether,the obtained solid is filtered off, washed with a small amount ofacetonitrile and finally with diethyl ether. The crude product (51-81%)can be recrystallized from acetonitrile to yield the purified product(34-73%).

C) In case the appropriate chloroformates are commercially available 1mmol of the chloroformate is reacted with 1 mmol of the amino buildingblock in pyridine. After the reaction is completed, the solvent isremoved and the remaining crude product purified as described above.

F. General Procedure for Thiocarbamate Formation

1 equivalent of the amine and 1.3 equivalents of the appropriatechlorothioformate are stirred in pyridine for 3 h at ambienttemperature. The mixture is concentrated and the thiocarbamate iscrystallized from ethanol and/or purified by flash chromatography onsilica gel.

FF. Alternative General Procedure for Thiocarbamate Formation

a) Preparation of the imidazole 1-carboxylic thioester reagents: Asolution of the appropriate thiol (10 mmol), 1,1′-carbonyldiimidazole(10 mmol) in abs. tetrahydrofurane (20 ml) is stirred at roomtemperature for 2 to 3 h, the reaction is monitored by TLC. The reactionmixture is extracted by three portions of 10% sodium hydrogencarbonatesolution and once by water. The organic layer is dried over sodiumsulfate, evaporated to yield a pale yellow oil or colorless solid.

b) Synthesis of thiocarbamates: To a suspension of the appropriate base(1 mmol) and reagent (1 mmole) in abs. dichloromethane (20 ml), DBU (1.2mmol) is added, the mixture is stirred for 1 to 2 days, the reaction ismonitored by TLC (silica, dichloromethane/ethyl acetate 10:1 mixture asan eluent, or, in some cases, ethyl acetate/methanol 1:1). The reactionmixture is extracted twice by 10% sodium hydrogencarbonate solution,once by water, and the organic layer is dried over sodium sulfate. Afterevaporation the residue is purified by column chromatography.

G. General Procedure for Urea Formation

1 equivalent of the amine and 1 equivalent of the appropriate isocyanateare stirred in dichloromethane over night at ambient temperature. Themixture is concentrated and the residue is subjected to flashchromatography on silica gel (eluent dichloromethane/methanol).

Alternatively, 1 equivalent of the amine, 1 equivalent ofN,N-carbonyldiimidazole and 1 equivalent of the second amine are stirredin a suitable solvent, e.g. dichloromethane, over night at ambienttemperature. The mixture is concentrated and the residue is subjected toflash chromatography on silica gel.

H. General Procedure for the Formation of Acrylic Acid/Cinnamic AcidDerivatives

The appropriate aldehyde and 1.3 eq triethylphosphonoacetate aredissolved in THF and 1 eq DBU is added at 0° C. After stirring untilcompletion of the reaction, 1N HCl (aq) is added and the reactionmixture extracted with dichloromethane. The organic layer is dried overMgSO₄ and the solvent removed. The crude ethyl ester is used for thenext reaction step.

The crude ethyl ester is suspended in 1N NaOH and the reaction mixturestirred until completion of the reaction (if necessary some THF isadded). Then 1N HC (is added until the reaction mixture is slightlyacidic and the mixture is extracted with diethylether. The ethereallayer is dried over MgSO₄ and the solvent removed. The crude acrylicacid/cinnamic acid derivative is used for the reactions mentionedherein.

It is to be stated, that the person skilled in the art can apply—on thebase of his/her expert knowledge, general art and/or analogous orsimilar art-known procedures—starting from the starting compounds, whichare mentioned herein or which can be prepared analogously to thementioned compounds, the general procedures described herein to thesynthesis of those specific examples mentioned herein and furtherspecific examples encompassed from the scope of the present invention.

COMMERCIAL APPLICABILITY

The compounds according to the present invention have miscellaneousvaluable pharmacological properties which can make them commerciallyapplicable.

The compounds according to the invention therefore can be employed astherapeutic agents for the treatment and prophylaxis of diseases inhuman and veterinary medicine.

Thus, for example, in more embodimental detail, the compounds accordingto this invention are potent and highly efficacious cell-cycle specificinhibitors of cellular (hyper)proliferation and/or inducers of apoptosisin cancer cells. Therefore, these compounds are expected to be usefulfor treating (hyper)proliferative diseases and/or disorders responsiveto the induction of apoptosis, in particular cancer.

Further on, these compounds can be useful in the treatment of benign ormalignant neoplasia. A “neoplasia” is defined by cells displayingaberrant cell proliferation and/or survival and/or a block indifferentiation. A “benign neoplasia” is described by hyperproliferationof cells, incapable of forming an aggressive, metastasizing tumorin-vivo. In contrast, a “malignant neoplasia” is described by cells withmultiple cellular and biochemical abnormalities, capable of forming asystemic disease, for example forming tumor metastasis in distantorgans.

Various diseases are caused by limitless replicative potential andaberrant cell proliferation (“hyperproliferation”) as well as evasionfrom apoptosis. These diseases include benign hypoplasia like that ofthe prostate (“BPH”) or colon epithelium. Most importantly thesediseases include malignant neoplasia commonly described as cancer andcharacterized by tumor cells finally metastasizing into distinct organsor tissues. Malignant neoplasia include solid and hematological tumors.Solid tumors are exemplified by tumors of the breast, bladder, bone,brain, central and peripheral nervous system, colon, endocrine glands(eg thyroid and adrenal cortex), esophagus, endometrium, germ cells,head and neck, kidney, liver, lung, larynx and hypopharynx,mesothelioma, sarcoma, ovary, pancreas, prostate, rectum, renal, smallintestine, soft tissue, testis, stomach, skin, ureter, vagina and vulva.Malignant neoplasia include inherited cancers exemplified byRetinoblastoma and Wilms tumor. In addition, malignant neoplasia includeprimary tumors in said organs and corresponding secondary tumors indistant organs (“tumor metastases”). Hematological tumors areexemplified by aggressive and indolent forms of leukemia and lymphoma,namely non-Hodgkins disease, chronic and acute myeloid leukemia(CML/AML), acute lymphoblastic leukemia (ALL), Hodgkins disease,multiple myeloma and T-cell lymphoma. Also included are myelodysplasticsyndrome, plasma cell neoplasia, paraneoplastic syndromes, cancers ofunknown primary site as well as AIDS related malignancies.

Compounds according to the present invention can be commerciallyapplicable for treatment, prevention or amelioration of the diseases ofbenign and malignant behavior as described before. Neoplastic cellproliferation might effect normal cell behaviour and organ function. Forexample the formation of new blood vessels, a process described asneovascularization, is induced by tumors or tumor metastases. Compoundsaccording to this invention can be commercially applicable for treatmentof pathophysiological relevant processes caused by benign or neoplasticcell proliferation, such as, but not limited to, neovascularization byunphysiological proliferation of vascular endothelial cells.

Drug resistance is of particular importance for the frequent failure ofstandard cancer therapeutics. This drug resistance is caused by variouscellular and molecular mechanisms like overexpression of drug effluxpumps or mutation within the cellular target protein. The commercialapplicability of compounds according to this invention is not limited to1^(st) line treatment of patients. Patients with resistance to definedcancer chemotherapeutics or target specific anti-cancer drugs (2^(nd) or3^(rd) line treatment) can be also amenable for treatment with compoundsaccording to this invention.

The compounds according to the present invention display a cell cycledependent cytotoxic activity, more precisely a mitosis confinedactivity, leading to a mitotic arrest which inevitably results in theonset of apoptosis and/or cell death.

In the context of their properties, functions and usabilities mentionedherein, the compounds according to the present invention are expected tobe distinguished by valuable and desirable effects related therewith,such as e.g. by low toxicity, superior bioavailability in general (suchas e.g. good enteral absorption), superior therapeutic window, absenceof significant side effects, and/or further beneficial effects relatedwith their therapeutic and pharmaceutical suitability.

The invention further includes a method for treating(hyper)proliferative diseases and/or disorders responsive to theinduction of apoptosis, particularly those diseases, disorders,conditions or illnesses mentioned above, in mammals, including humans,suffering therefrom comprising administering to said mammals in needthereof a pharmacologically active and therapeutically effective andtolerable amount of one or more of the compounds according to thisinvention.

The present invention further includes a method useful to modulateapoptosis and/or aberrant cell growth in the therapy of benign ormalignant neoplastic diseases, such as e.g. cancer, comprisingadministering to a subject in need of such therapy a pharmacologicallyactive and therapeutically effective and tolerable amount of one or moreof the compounds according to this invention.

The present invention further relates to the use of the compoundsaccording to this invention for the production of pharmaceuticalcompositions which are employed for the treatment, prophylaxis,inhibition and/or amelioration of the illnesses mentioned.

The present invention further relates to the use of the compoundsaccording to this invention for the production of pharmaceuticalcompositions which can be used in the treatment, prevention oramelioration of (hyper)proliferative diseases of benign or malignantbehaviour and/or disorders responsive to the induction of apoptosis in amammal, such as, for example, benign or malignant neoplasia, e.g.cancer.

The present invention further relates to the use of the compoundsaccording to this invention for the production of pharmaceuticalcompositions which can be used use in the treatment, prevention oramelioration of disorders responsive to arresting aberrant cell growthand/or induction of apoptosis.

The present invention further relates to pharmaceutical compositionscomprising one or more of the compounds according to this invention anda pharmaceutically acceptable carrier or diluent.

The present invention further relates to pharmaceutical compositionsmade by combining one or more of the compounds according to thisinvention and a pharmaceutically acceptable carrier or diluent.

The present invention further relates to combinations comprising one ormore of the compounds according to this invention and pharmaceuticallyacceptable auxiliaries, excipients or vehicles, e.g. for use in thetreatment, prevention or amelioration of benign or malignant neoplasia,such as e.g. cancer.

The present invention further relates to a composition consistingessentially of a therapeutically effective and tolerable amount of oneor more tetrahydropyridothiophene compounds according to this inventiontogether with the usual pharmaceutically acceptable vehicles, diluentsand/or excipients for use in therapy, e.g. for treating, preventing orameliorating hyperproliferative diseases, such as e.g. cancer, and/ordisorders responsive to induction of apoptosis.

The present invention further relates to compounds according to thisinvention for use in therapy, such as, for example, in the treatment,prevention or amelioration of (hyper)proliferative diseases of benign ormalignant behaviour and/or disorders responsive to the induction ofapoptosis, such as e.g. those diseases mentioned herein, particularlycancer.

The present invention further relates to compounds according to thisinvention having anti-proliferative and/or apoptosis inducing activity.

The present invention further relates to pharmaceutical compositionsaccording to this invention having anti-proliferative activity.

The present invention further relates to pharmaceutical compositionsaccording to this invention having apoptosis inducing activity.

The invention further relates to the use of a pharmaceutical compositioncomprising one or more of the compounds according to this invention assole active ingredient(s) and a pharmaceutically acceptable carrier ordiluent in the manufacture of pharmaceutical products for the treatmentand/or prophylaxis of the illnesses mentioned above.

Additionally, the invention relates to an article of manufacture, whichcomprises packaging material and a pharmaceutical agent contained withinsaid packaging material, wherein the pharmaceutical agent istherapeutically effective inhibiting cellular (hyper)proliferationand/or inducing apoptosis, ameliorating the symptoms of a(hyper)proliferative disorder and/or a disease responsive to theinduction of apoptosis, and wherein the packaging material comprises alabel or package insert which indicates that the pharmaceutical agent isuseful for preventing or treating a (hyper)proliferative disorder and/ora diseases responsive to the induction of apoptosis, and wherein saidpharmaceutical agent comprises one or more compounds according to theinvention. The packaging material, label and package insert otherwiseparallel or resemble what is generally regarded as standard packagingmaterial, labels and package inserts for pharmaceuticals having relatedutilities.

The pharmaceutical compositions according to this invention can beprepared by processes which are known per se and familiar to the personskilled in the art. As pharmaceutical compositions, the compounds of theinvention (=active compounds) are

either employed as such, or preferably in combination with suitablepharmaceutical auxiliaries and/or excipients, e.g. in the form oftablets, coated tablets, capsules, caplets, suppositories, patches (e.g.as TTS), emulsions, suspensions, gels or solutions, the active compoundcontent advantageously being between 0.1 and 95% and where, by theappropriate choice of the auxiliaries and/or excipients, apharmaceutical administration form (e.g. a delayed release form or anenteric form) exactly suited to the active compound and/or to thedesired onset of action can be achieved.

The person skilled in the art is familiar with auxiliaries, vehicles,excipients, diluents, carriers or adjuvants which are suitable for thedesired pharmaceutical formulations, preparations or compositions onaccount of his/her expert knowledge. In addition to solvents, gelformers, ointment bases and other active compound excipients, forexample antioxidants, dispersants, emulsifiers, preservatives,solubilizers, colorants, complexing agents or permeation promoters, canbe used.

Depending upon the particular disease, to be treated or prevented,additional therapeutic active agents, which are normally administered totreat or prevent that disease, may optionally be coadministered with thecompounds according to this invention. As used herein, additionaltherapeutic agents that are normally administered to treat or prevent aparticular disease are known as appropriate for the disease beingtreated.

For example, compounds according to this invention may be combined withone or more standard therapeutic agents used for treatment of thediseases as mentioned before.

In one particular embodiment, compounds according to this invention maybe combined with one or more art-known anti-cancer agents, such as e.g.with one or more chemotherapeutic and/or target specific anti-canceragents as described below.

Examples of known chemotherapeutic anti-cancer agents frequently usedfor combination therapy include, but not are limited to (i)alkylating/carbamoylating agents such as Cyclophosphamide (Endoxan®),Ifosfamid (Holoxan®), Thiotepa (Thiothepa Lederle®), Melphalan(Alkeran®), or chloroethylnitrosourea (BCNU); (ii) platinum derivativeslike cis-platin (Platinex® BMS), oxaliplatin or carboplatin (Carboplat®BMS); (iii) antimitotic agents/tubulin inhibitors such as vincaalkaloids (vincristine, vinblastine, vinorelbine), taxanes such as Taxol(Paclitaxel®), Taxotere (Docetaxel®) and analogs as well as newformulations and conjugates thereof; (iv) topoisomerase inhibitors suchas anthracyclines such as Doxorubicin (Adriblastin®),epipodophyllotoxines (such as Etoposide (Etopophos®) and camptothecinanalogs such as Topotecan (Hycamtin®); (v) pyrimidine antagonists suchas 5-fluorouracil (5-FU), Capecitabine (Xeloda®),Arabinosylcytosine/Cytarabin (Alexan®) or Gemcitabine (Gemzar®); (vi)purin antagonists such as 6-mercaptopurine (Puri-Nethol®), 6-thioguanineor fludarabine (Fludara®) and finally (vii) folic acid antagonists suchas methotrexate (Farmitrexat®) and pernetrexed (Alimta®).

Examples of target specific anti-cancer drug classes used inexperimental or standard cancer therapy include but are not limited to(i) kinase inhibitors such as e.g. Glivec (Imatinib®), ZD-1839/Iressa(Gefitinib®), Bay43-9006 (Sorafenib®), SU11248 (Sutent®) orOSI-774/Tarceva (Erlotinib®); (ii) proteasome inhibitors such as PS-341(Velcade®); (iii) histone deacetylase inhibitors like SAHA, PXD101,MS275, MGCD0103, Depsipeptide/FK228, NVP-LBH589, Valproic acid (VPA) andbutyrates; (iv) heat shock protein inhibitors like17-allylaminogeldanamycin (17-AAG); (v) vascular targeting agents (VAT)and anti-angiogenic drugs like the VEGF antibody Avastin (Bevacizumab®)or the KDR tyrosine kinase inhibitor PTK787/ZK222584 (Vatalanib®); (vi)monoclonal antibodies such as Herceptin (Trastuzumab®) orMabThera/Rituxan (Rituximab®) or C225/Erbitux (Cetuximab®) as well asmutants and conjugates of monoclonal antibodies and antibody fragments;(vii) oligonucleotide based therapeutics like G-3139/Genasense(Oblimersen®); (viii) protease inhibitors (ix) hormonal therapeuticssuch as anti-estrogens (e.g. Tamoxifen), anti-androgens (e.g. Flutamideor Casodex), LHRH analogs (e.g. Leuprolide, Goserelin or Triptorelin)and aromatase inhibitors.

Other known anti-cancer agents which can be used for combination therapyinclude bleomycin, retinoids such as all-trans retinoic acid (ATRA), DNAmethyltransferase inhibitors such as the 2-deoxycytidine derivativeDecitabine (Docagen®), alanosine, cytokines such as interleukin-2 orinterferons such as interferon α2 or interferon-γ, TRAIL, DR4/5agonistic antibodies, FasL- and TNF-R agonists.

As exemplary chemotherapeutic/anti-cancer agents, which can be useful inthe combination therapy according to the present invention the followingdrugs may be mentioned, without being restricted thereto, 5 FU,actinomycin D, ABARELIX, ABCIXIMAB, ACLARUBICIN, ADAPALENE, ALEMTUZUMAB,ALTRETAMINE, AMINOGLUTETHIMIDE, AMIPRILOSE, AMRUBICIN, ANASTROZOLE,ANCITABINE, ARTEMISININ, AZATHIOPRINE, BASILIXI MAB, BEN DAMUSTINE,BEXXAR, BICALUTAMIDE, BLEOMYCIN, BROXURIDINE, BUSULFAN, CAPECITABINE,CARBOPLATIN, CARBOQUONE, CARMUSTINE, CETRORELIX, CHLORAMBUCIL,CHLORMETHINE, CISPLATIN, CLADRIBINE, CLOMIFENE, CYCLOPHOSPHAMIDE,DACARBAZINE, DACLIZUMAB, DACTINOMYCIN, DAUNORUBICIN, DESLORELIN,DEXRAZOXANE, DOCETAXEL, DOXIFLURIDINE, DOXORUBICIN, DROLOXIFENE,DROSTANOLONE, EDELFOSINE, EFLORNITHINE, EMITEFUR, EPIRUBICIN,EPITIOSTANOL, EPTAPLATIN, ERBITUX, ESTRAMUSTINE, ETOPOSIDE, EXEMESTANE,FADROZOLE, FINASTERIDE, FLOXURIDINE, FLUCYTOSINE, FLUDARABINE,FLUOROURACIL, FLUTAMIDE, FORMESTANE, FOSCARNET, FOSFESTROL, FOTEMUSTINE,FULVESTRANT, GEFITINIB, GEMCITABINE, GLIVEC, GOSERELIN, GUSPERIMUS,HERCEPTIN, IDARUBICIN, IDOXURIDINE, IFOSFAMIDE, IMATINIB, IMPROSULFAN,INFLIXIMAB, IRINOTECAN, LANREOTIDE, LETROZOLE, LEUPRORELIN, LOBAPLATIN,LOMUSTINE, MELPHALAN, MERCAPTOPURINE, METHOTREXATE, METUREDEPA,MIBOPLATIN, MIFEPRISTONE, MILTEFOSINE, MIRIMOSTIM, MITOGUAZONE,MITOLACTOL, MITOMYCIN, MITOXANTRONE, MIZORIBINE, MOTEXAFIN,NARTOGRASTIM, NEBAZUMAB, NEDAPLATIN, NILUTAMIDE, NIMUSTINE, OCTREOTIDE,ORMELOXIFENE, OXALIPLATIN, PACLITAXEL, PALIVIZUMAB, PEGASPARGASE,PEGFILGRASTIM, PENTETREOTIDE, PENTOSTATIN, PERFOSFAMIDE, PIPOSULFAN,PIRARUBICIN, PLICAMYCIN, PREDNIMUSTINE, PROCARBAZINE, PROPAGERMANIUM,PROSPIDIUM CHLORIDE, RALTITREXED, RANIMUSTINE, RANPIRNASE, RASBURICASE,RAZOXANE, RITUXIMAB, RIFAMPICIN, RITROSULFAN, ROMURTIDE, RUBOXISTAURIN,SARGRAMOSTIM, SATRAPLATIN, SIROLIMUS, SOBUZOXANE, SPIROMUSTINE,STREPTOZOCIN, TAMOXIFEN, TASONERMIN, TEGAFUR, TEMOPORFIN, TEMOZOLOMIDE,TENIPOSIDE, TESTOLACTONE, THIOTEPA, THYMALFASIN, TIAMIPRINE, TOPOTECAN,TOREMIFENE, TRASTUZUMAB, TREOSULFAN, TRIAZIQUONE, TRIMETREXATE,TRIPTORELIN, TROFOSFAMIDE, UREDEPA, VALRUBICIN, VERTEPORFIN,VINBLASTINE, VINCRISTINE, VINDESINE, VINORELBINE, VOROZOLE, and ZEVALIN.

The person skilled in the art is aware on the base of his/her expertknowledge of the total daily dosage(s) and administration form(s) of theadditional therapeutic agent(s) coadministered. Said total dailydosage(s) can vary within a wide range.

In practicing the present invention, the compounds according to thisinvention may be administered in combination therapy separately,sequentially, simultaneously or chronologically staggered (such as e.g.as combined unit dosage forms, as separate unit dosage forms, asadjacent discrete unit dosage forms, as fixed or non-fixed combinations,as kit-of-parts or as admixtures) with one or more standardtherapeutics, in particular art-known anti-cancer agents, such as e.g.those mentioned above.

In this context, the present invention further relates to a combinationcomprising

-   a first active ingredient, which is at least one    tetrahydropyridothiophene compound according to this invention, and-   a second active ingredient, which is at least one art-known    anti-cancer agent, such as e.g. one or more of those mentioned    herein above,-   for separate, sequential, simultaneous or chronologically staggered    use in therapy, such as e.g. in therapy of those diseases mentioned    herein.

The term “combination” according to this invention may be present as afixed combination, a non-fixed combination or a kit-of-parts.

A “fixed combination” is defined as a combination wherein the said firstactive ingredient and the said second active ingredient are presenttogether in one unit dosage or in a single entity. One example of a“fixed combination” is a pharmaceutical composition wherein the saidfirst active ingredient and the said second active ingredient arepresent in admixture for simultaneous administration, such as in aformulation. Another example of a “fixed combination” is apharmaceutical combination wherein the said first active ingredient andthe said second active ingredient are present in one unit without beingin admixture.

A “kit-of-parts” is defined as a combination wherein the said firstactive ingredient and the said second active ingredient are present inmore than one unit. One example of a “kit-of-parts” is a combinationwherein the said first active ingredient and the said second activeingredient are present separately. The components of the kit-of-partsmay be administered separately, sequentially, simultaneously orchronologically staggered.

The present invention further relates to a pharmaceutical compositioncomprising

-   a first active ingredient, which is at least one    tetrahydropyridothiophene compound according to this invention, and-   a second active ingredient, which is at least one art-known    anti-cancer agent, such as e.g. one or more of those mentioned    herein above, and, optionally,-   a pharmaceutically acceptable carrier or diluent, for separate,    sequential, simultaneous or chronologically staggered use in    therapy.

The present invention further relates to a combination productcomprising

-   a.) at least one compound according to this invention formulated    with a pharmaceutically acceptable carrier or diluent, and-   b.) at least one art-known anti-cancer agent, such as e.g. one or    more of those mentioned herein above, formulated with a    pharmaceutically acceptable carrier or diluent.

The present invention further relates to a kit-of-parts comprising apreparation of a first active ingredient, which is atetrahydropyridothiophene compound according to this invention, and apharmaceutically acceptable carrier or diluent; a preparation of asecond active ingredient, which is an art-known anti-cancer agent, suchas one of those mentioned above, and a pharmaceutically acceptablecarrier or diluent; for simultaneous, sequential, separate orchronologically staggered use in therapy. Optionally, said kit comprisesinstructions for its use in therapy, e.g. to treat hyperproliferativediseases and/or disorders responsive to the induction of apoptosis, suchas e.g. cancer.

The present invention further relates to a combined preparationcomprising at least one compound according to this invention and atleast one art-known anti-cancer agent for simultaneous, sequential orseparate administration.

The present invention further relates to pharmaceutical compositions orcombinations according to the present invention havinganti-proliferative and/or apoptosis inducing properties.

In addition, the present invention further relates to a method fortreating in combination therapy (hyper)proliferative diseases and/ordisorders responsive to the induction of apoptosis, such as e.g. cancer,in a patient comprising administering a combination, composition,formulation, preparation or kit as described herein to said patient inneed thereof.

In addition, the present invention further relates to a method fortreating (hyper)proliferative diseases of benign or malignant behaviourand/or disorders responsive to the induction of apoptosis, such as e.g.cancer, in a patient comprising administering in combination therapyseparately, simultaneously, sequentially or chronologically staggered apharmaceutically active and therapeutically effective and tolerableamount of a pharmaceutical composition, which comprises atetrahydropyridothiophene compound according to this invention and apharmaceutically acceptable carrier or diluent, and a pharmaceuticallyactive and therapeutically effective and tolerable amount of one or moreart-known anti-cancer agents, such as e.g. one or more of thosementioned herein, to said patient in need thereof.

In addition, the present invention further relates to the use of acomposition, combination, formulation, preparation or kit according tothis invention in the manufacture of a pharmaceutical product, such ase.g. a commercial package or a medicament, for treating, preventing orameliorating (hyper)proliferative diseases, such as e.g. cancer, and/ordisorders responsive to the induction of apoptosis, particularly thosediseases mentioned herein, such as e.g. malignant or benign neoplasia.

The present invention further relates to a commercial package comprisingone or more compounds of the present invention together withinstructions for simultaneous, sequential or separate use with one ormore chemotherapeutic and/or target specific anti-cancer agents, such ase.g. any of those mentioned herein.

The present invention further relates to a commercial package consistingessentially of one or more compounds of the present invention as soleactive ingredient together with instructions for simultaneous,sequential or separate use with one or more chemotherapeutic and/ortarget specific anti-cancer agents, such as e.g. any of those mentionedherein.

The present invention further relates to a commercial package comprisingone or more chemotherapeutic and/or target specific anti-cancer agents,such as e.g. any of those mentioned herein, together with instructionsfor simultaneous, sequential or separate use with one or moretetrahydropyridothiophene compounds according to the present invention.

The compositions, combinations, preparations, formulations, kits orpackages mentioned in the context of the combination therapy accordingto this invention may also include more than one of the compoundsaccording to this invention and/or more than one of the art-knownanti-cancer agents mentioned.

The first and second active ingredient of a combination or kit-of-partsaccording to this invention may be provided as separate formulations(i.e. independently of one another), which are subsequently broughttogether for simultaneous, sequential, separate or chronologicallystaggered use in combination therapy; or packaged and presented togetheras separate components of a combination pack for simultaneous,sequential, separate or chronologically staggered use in combinationtherapy.

The type of pharmaceutical formulation of the first and second activeingredient of a combination or kit-of-parts according to this inventioncan be similar, i.e. both ingredients are formulated in separate tabletsor capsules, or can be different, i.e. suited for differentadministration forms, such as e.g. one active ingredient is formulatedas tablet or capsule and the other is formulated for e.g. intravenousadministration.

The amounts of the first and second active ingredients of thecombinations, compositions or kits according to this invention maytogether comprise a therapeutically effective amount for the treatment,prophylaxis or amelioration of a (hyper)proliferative diseases and/or adisorder responsive to the induction of apoptosis, particularly one ofthose diseases mentioned herein.

In addition, compounds according to the present invention can be used inthe pre- or post-surgical treatment of cancer.

In further addition, compounds of the present invention can be used incombination with radiation therapy.

A combination according to this invention can refer to a compositioncomprising both the compound(s) according to this invention and theother active anti-cancer agent(s) in a fixed combination (fixed unitdosage form), or a medicament pack comprising the two or more activeingredients as discrete separate dosage forms (non-fixed combination).In case of a medicament pack comprising the two or more activeingredients, the active ingredients are preferably packed into blistercards which are suited for improving compliance.

Each blister card preferably contains the medicaments to be taken on oneday of treatment. If the medicaments are to be taken at different timesof day, the medicaments can be disposed in different sections on theblister card according to the different ranges of times of day at whichthe medicaments are to be taken (for example morning and evening ormorning, midday and evening). The blister cavities for the medicamentsto be taken together at a particular time of day are accommodated in therespective range of times of day. The various times of day are, ofcourse, also put on the blister in a clearly visible way. It is alsopossible, of course, for example to indicate a period in which themedicaments are to be taken, for example stating the times.

The daily sections may represent one line of the blister card, and thetimes of day are then identified in chronological sequence in thiscolumn.

Medicaments which must be taken together at a particular time of day areplaced together at the appropriate time on the blister card, preferablya narrow distance apart, allowing them to be pushed out of the blistereasily, and having the effect that removal of the dosage form from theblister is not forgotten.

The administration of the pharmaceutical compositions or combinationsaccording to the invention may be performed in any of the generallyaccepted modes of administration available in the art. Illustrativeexamples of suitable modes of administration include intravenous, oral,nasal, parenteral, topical, transdermal and rectal delivery. Oral andintravenous delivery are preferred.

For the treatment of dermatoses, the compounds of the invention can bein particular administered in the form of those pharmaceuticalcompositions which are suitable for topical application. For theproduction of the pharmaceutical compositions, the compounds of theinvention (=active compounds) are preferably mixed with suitablepharmaceutical auxiliaries and further processed to give suitablepharmaceutical formulations. Suitable pharmaceutical formulations are,for example, powders, emulsions, suspensions, sprays, oils, ointments,fatty ointments, creams, pastes, gels or solutions. The pharmaceuticalcompositions according to the invention can be prepared by processesknown per se.

The dosage of the active compounds is carried out in the order ofmagnitude customary for inhibitors for cellular proliferation orapoptosis inducers. Topical application forms (such as ointments) forthe treatment of dermatoses thus contain the active compounds in aconcentration of, for example, 0.1-99%. The customary dose in the caseof systemic therapy (p.o.) is between 0.3 and 30 mg/kg per day, (i. v.)is between 0.3 and 30 mg/kg/h.

The choice of the optimal dosage regime and duration of medication,particularly the optimal dose and manner of administration of the activecompounds necessary in each case can be determined by a person skilledin the art on the basis of his/her expert knowledge.

Biological Investigations

The anti-proliferative/cytotoxic activity of the compounds describedherein, can be tested on subclones of RKO (RKOp27) human colonadenocarcinoma cells (Schmidt et al., Oncogene 19, 2423-2429; 2000)using the Alamar Blue cell viability assay (described in O'Brien et al.Eur J Biochem 267, 5421-5426, 2000). The compounds are dissolved as 20mM solutions in dimethylsulfoxide (DMSO) and subsequently diluted insemi-logarithmic steps. DMSO dilutions are further diluted 1:100 intoDulbecco's modified Eagle's medium (DMEM) containing 10% fetal calfserum to a final concentration twice as much as the final concentrationin the test. RKO subclones are seeded into 96 well flat bottom plates ata density of 4000 cells per well in a volume of 50 μl per well. 24 hoursafter seeding 50 μl each of the compound dilutions in DMEM are addedinto each well of the 96 well plate. Each compound dilution is tested asquadruplicates. Wells containing untreated control cells are filled with50 μl DMEM containing 1% DMSO. The cells are then incubated with thesubstances for 72 hours at 37° C. in a humidified atmosphere containing5% carbon dioxide. To determine the viability of the cells, 10 μl of anAlamar Blue solution (Biosource) are added and the fluorescence ismeasured at an extinction of 544 nm and an emission of 590 nm. For thecalculation of the cell viability the emission value from untreatedcells is set as 100% viability and the emission rates of treated cellsare set in relation to the values of untreated cells. Viabilities areexpressed as % values.

The corresponding IC₅₀ values of the compounds foranti-proliferative/cytotoxic activity are determined from theconcentration-effect curves.

Representative IC₅₀ values for anti-proliferation/cytotoxicitydetermined in the aforementioned assay are described in the table A(1^(st) column), in which the numbers of the compound correspond to thenumbers of the examples.

Any or all of the compounds according to the present invention which arelisted in the Table A, as well as their salts, are to be mentioned as aparticular interesting subject of the present invention.

TABLE A Anti-proliferative/cytotoxic activity IC₅₀ RKO p27 IC₅₀ RKO p27arrested Compound proliferating [μM] [μM] 1 <1 >100 2, 4, 7 to 14, 16,The IC₅₀ values of The IC₅₀ 19 to 21, 23, 24, these listed values of 26to 30, 32 to compounds are all these listed 39, 43 to 45, and ≦2compounds 47 are all >100 48 to 50, 53, 55, 57, 59 to 62, 64 to The IC₅₀values of The IC₅₀ 68, 70 to 76, 78 to 80, 82, 83, 85, these listedvalues of 86, 89 to 91, 95 to 98, 100, 102 to compounds are all theselisted 104, 106, 108, 111, 112, 114, 116 ≦2 compounds to 118, 120, 122,125 to 129, 133 are all ≧100 to 140, 142 to 144, 146 to 152, 154 to 156,158 to 162, 164, 166, 167, 169 to 172, 174 to 178, 181, 183, 185 to 196,198, 200, 205, 206, 209 to 212, 214 to 219, 221, 223, 224, 226 to 232,and 234 to 243 54, 69, 77, 84, 88, 99, 113, 124, The IC₅₀ values of TheIC₅₀ 145, 157, 168, 182, 220, 222, and these listed values of 233compounds are all these listed ≦0.5 compounds are all ≧50

To determine the cell cycle specific mode of action, subclones of RKOcolon adenocarcinoma cells (RKOp27 or RKOp21 as described by Schmidt etal. in Oncogene 19, 2423-2429; 2000) are seeded into 96 well flat bottomplates at a density of 16000 cells per well in a volume of 50 μl perwell in DMEM growth medium with 10% FCS containing 10 μM Ponasterone A.24 hours after seeding 50 μl each of the compound dilutions in DMEM areadded into each well of the 96 well plate. Each compound dilution istested as quadruplicates. Wells containing untreated control cells arefilled with 50 μl DMEM containing 1% DMSO. The cells are then incubatedwith the substances for 72 hours at 37° C. in a humidified atmospherecontaining 5% carbon dioxide. To determine the viability of the cells,10 μl of an Alamar Blue solution (Biosource) are added and thefluorescence is measured at an extinction of 544 nm and an emission of590 nm. For the calculation of the cell viability the emission valuefrom untreated cells is set as 100% viability and the emission rates oftreated cells are set in relation to the values of untreated cells.Viabilities are expressed as % values. Viability is compared ofproliferating cells grown in the absence of the inducer Ponasterone A,versus viability of cells arrested by the expression of ectopic p27Kip1induced by Ponasterone A. The data of this experimental setting aresummarized in table A (2^(nd) column).

To test the anti-proliferative activity/cytotoxicity on cells known tobe highly resistant towards distinct classes of chemotherapeutics, HCT15cells (with P-glycoprotein overexpression) and MCF7 ADR cells, both ofthem are known to overexpress certain classes of multidrug resistancetransporters are used in Alamar Blue assays as described above. Briefly,the compounds are dissolved as 20 mM solutions in dimethylsulfoxide(DMSO) and subsequently diluted in semi-logarithmic steps. DMSOdilutions are further diluted 1:100 into DMEM containing 10% fetal calfserum to a final concentration twice as much as the final concentrationin the test. The cells to be tested are seeded into 96 well flat bottomplates at a density of 10000 cells per well in a volume of 50 μl perwell. 24 hours after seeding 50 μl each of the compound dilutions inDMEM are added into each well of the 96 well plate. Each compounddilution is tested as quadruplicates. Wells containing untreated controlcells are filled with 50 μl DMEM containing 1% DMSO. The cells are thenincubated with the substances for 72 hours at 37° C. in a humidifiedatmosphere containing 5% carbon dioxide. To determine the viability ofthe cells, 10 μl of an Alamar Blue solution (Biosource) are added andthe fluorescence is measured at an extinction of 544 nm and an emissionof 590 nm. For the calculation of the cell viability the emission valuefrom untreated cells is set as 100% viability and the emission rates oftreated cells are set in relation to the values of untreated cells.Viabilities are expressed as % values.

The induction of apoptosis can be measured by using a cell deathdetection ELISA (Roche Biochemicals, Mannheim, Germany). RKO subclonesare seeded into 96 well flat bottom plates at a density of 10000 cellsper well in a volume of 50 μl per well. 24 hours after seeding 50 μleach of the compound dilutions in DMEM are added into each well of the96 well plate. Each compound dilution is tested at least as triplicates.Wells containing untreated control cells are filled with 50 μl DMEMcontaining 1% DMSO. The cells are then incubated with the substances for24 hours at 37° C. in a humidified atmosphere containing 5% carbondioxide. As a positive control for the induction of apoptosis, cells aretreated with 50 μM Cisplatin (Gry Pharmaceuticals, Kirchzarten,Germany). Medium is then removed and the cells are lysed in 200 μl lysisbuffer. After centrifugation as described by the manufacturer, 10 μl ofcell lysate is processed as described in the protocol. The degree ofapoptosis is calculated as follows: The absorbance at 405 nm obtainedwith lysates from cells treated with 50 μM cisplatin is set as 100 cpu(cisplatin units), while an absorbance at 405 nm of 0.0 is set as 0.0cpu. The degree of apoptosis is expressed as cpu in relation to thevalue of 100 cpu reached with the lysates obtained from cells treatedwith 50 μM cisplatin.

The mitotis-confined activity can be measured using a methylenblue/eosin staining kit (Merck, Darmstadt, Germany). RKO subclones areseeded into 6 well tissue culture plates at a density of 200000 cellsper well in a volume of 2 ml per well. 24 hours after seeding each ofthe compound dilutions in DMEM containing up to 1% DMSO are added ontoeach 6 well plate. The cells are then incubated with the substances for24 hours at 37° C. in a humidified atmosphere containing 5% carbondioxide. As a positive control for the induction of mitosis, the cellsare treated with 20 nM vincristine or paclitaxel. The cells are thenharvested by trypsinization and subsequent centrifugation, and washedonce with phosphate-buffered saline. Subsequently, the cells arecentrifuged on microscope slides for 1 min at 1200 rpm using a cytospin.Cells are then fixed with methanol and stained with methylen blue andeosin according to the manufacturer's recommendations. Mitotic figurescan then be visualized by standard microscopy.

Another method to determine the mitosis confined activity can beimmunoblotting of cell extracts with an antibody specific forphosphorylated histone H3, which is a generally accepted marker ofmitosis. RKO subclones are seeded into 6 well tissue culture plates at adensity of 200000 cells per well in a volume of 2 ml per well. 24 hoursafter seeding each of the compound dilutions in DMEM containing up to 1%DMSO are added onto each 6 well plate. The cells are then incubated withthe substances for another 24 hours at 37° C. in a humidified atmospherecontaining 5% carbon dioxide. As a positive control for the induction ofmitosis, the cells are treated with 20 nM vincristine or paclitaxel. Thecells are then harvested by trypsinization and subsequentcentrifugation, and washed once with phosphate-buffered saline.Subsequently, the cells are lysed in a lysis buffer containing 50 mMTris, pH 7A, 150 mM NaCl, 1% NP40, 50 mM NaF, 1 mM Na₃VO₄, 1 mMphenylmethylsulfonyl fluoride. The lysates are cleared by centrifugationand the supernatants are collected. Equal amounts of lysate protein areseparated in an SDS-polyacrylamide electrophoresis using 12.5% gels andsubsequently blotted on immobilon membranes (Millipore, schwalbach,Germany). After blocking unspecific binding sites by incubation of themembrane in 3% bovine serum albumine in tris-buffered saline containing0.05% tween 20, antibodies specific for phospho-histone H3 (CellSignaling Technology, Beverly, USA) were added for 1 hour. Afterintensive washing with tris-buffered saline containing 0.05% tween 20,specific signals were visualized using a horseradish-peroxidase-coupledsecondary antibody and the use of the ECL chemoluminescence detectionkit (Amersham, Braunschweig, Germany) according to the manufacturer'srecommendations.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 depicts the compound of formula I.

1. A compound of formula I

wherein Ra is —C(O)R1, —C(O)OR2, —C(O)SR2, —C(O)N(R3)R4, —S(O)₂R1, or—S(O)₂N(R3)R4; Rb is Q-2-4C-alkenyl, in which Q is optionallysubstituted by Rba and/or Rbb and/or Rbc, and is phenyl or naphthyl, orQ is optionally substituted by Rca and/or Rcb, and is Har, or Q is Cyc;in which R1, R2 and R3 are the same or different and are independentlyselected from the group consisting of: hydrogen, 1-7C-alkyl,3-7C-cycloalkyl, Ar, Har and Het, wherein each of said 1-7C-alkyl,3-7C-cycloalkyl, Ar, Har and Het is unsubstituted or substituted by atleast one substituent independently selected from R5; each R4 isindependently selected from the group consisting of: hydrogen,1-7C-alkyl and 3-7C-cycloalkyl, wherein each of said 1-7C-alkyl and3-7C-cycloalkyl is unsubstituted or substituted by at least onesubstituent independently selected from R5; R5, Rba, Rbb, Rbc, Rca andRcb are the same or different and are independently selected from thegroup consisting of: 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har, Het, halogen,trifluoromethyl, nitro, cyano, guanidino, amidino, —C(O)R6, —C(O)OR7,—C(O)N(R8)R9, —S(O)₂R6, —S(O)₂N(R8)R9, —N(R10)C(O)R6, —N(R10)C(O)OR7,—N(R10)C(O)N(R8)R9, —N(R10)S(O)₂R6, —N(R10)S(O)₂N(R8)R9, —OC(O)R6,—OC(O)N(R8)R9, —OR7, —N(R8)R9 and —SR7, wherein each of said 1-7C-alkyl,3-7C-cycloalkyl, Ar, Har and Het is unsubstituted or substituted by atleast one substituent independently selected from R11; R6, R7 and R8 arethe same or different and are independently selected from the groupconsisting of: hydrogen, 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het,wherein each of said 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het isunsubstituted or substituted by at least one substituent independentlyselected from R12; each R9 is independently selected from the groupconsisting of: hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl, wherein each ofsaid 1-7C-alkyl and 3-7C-cycloalkyl is unsubstituted or substituted byat least one substituent independently selected from R12; each R10 isindependently selected from the group consisting of: hydrogen,1-7C-alkyl and 3-7C-cycloalkyl; R11 is R5; each R12 is independentlyselected from R5; each Ar is independently selected from the groupconsisting of phenyl and naphthyl; each Har is the same or different andindependently a fully aromatic or partially aromatic mono- or fusedbicyclic ring or ring system, which contains at least one heteroatom inthe ring or ring system, made up of a first constituent being a 5- or6-membered monocyclic unsaturated, aromatic heteroaryl ring A, whichheteroaryl ring A comprises at least one heteroatom independentlyselected from the group consisting of nitrogen, oxygen and sulfur, and,optionally, fused to said first constituent, a second constituent beinga benzene ring, a 5-6C-cycloakane ring, an additional heteroaryl ring A,or a heterocyclic ring B, wherein said Har is attached via asubstitutable ring carbon or ring nitrogen atom of Har; each Het isindependently a fully saturated or partially unsaturated mono- or fusedbicyclic ring or ring system made up of a first constituent being a 3-to 7-membered monocyclic fully saturated or partially unsaturated,non-aromatic heterocyclic ring B, wherein the heterocyclic ring Bcomprises one to three heteroatoms independently selected from the groupconsisting of nitrogen, oxygen and sulfur, and which heterocyclic ring Bis optionally substituted by one or two oxo groups, and, optionally,fused to said first constituent, a second constituent being a benzogroup, a 3-7C-cycloalkane group, or an additional heterocyclic ring B,wherein said Het ring or ring system is attached via a substitutablering carbon or ring nitrogen atom; Cyc is optionally substituted byhalogen on its benzene ring, and is a group of formula A

in which G is optionally substituted by Rda and/or Rdb, and is a 5- or6-membered saturated heterocyclic ring comprising one or two heteroatomsindependently selected from the group consisting of nitrogen, oxygen andsulfur, in which Rda is 1-4C-alkyl or halogen, Rdb is 1-4C-alkyl orhalogen, wherein said Cyc ring system is attached via a substitutablebenzoring carbon atom, or a salt thereof.
 2. A compound of formula Iaccording to claim 1, wherein Ra is —C(O)R1, —C(O)OR2, —C(O)SR2,—C(O)N(R3)R4, —S(O)₂R1, or —S(O)₂N(R3)R4; Rb is Q-2-4C-alkenyl, in whichQ is optionally substituted by Rba and/or Rbb and/or Rbc, and is phenylor naphthyl, or Q is optionally substituted by Rca and/or Rcb, and isHar, or Q is Cyc; in which R1, R2 and R3 are the same or different andare independently selected from the group consisting of: hydrogen,1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het, wherein each of said1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het is unsubstituted orsubstituted by at least one substituent independently selected from R5;each R4 is independently selected from the group consisting of:hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl, wherein each of said1-7C-alkyl and 3-7C-cycloalkyl is unsubstituted or substituted by atleast one substituent independently selected from R5; R5, Rba, Rbb, Rbc,Rca and Rcb are the same or different and are independently selectedfrom the group consisting of: 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har, Het,halogen, trifluoromethyl, nitro, cyano, guanidino, amidino, —C(O)R6,—C(O)OR7, —C(O)N(R8)R9, —S(O)₂R6, —S(O)₂N(R8)R9, —N(R10)C(O)R6,—N(R10)C(O)OR7, —N(R10)C(O)N(R8)R9, —N(R10)S(O)₂R6, —N(R10)S(O)₂N(R8)R9,—OC(O)R6, —OC(O)N(R8)R9, —OR7, —N(R8)R9 and —SR7, wherein each of said1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het is unsubstituted orsubstituted by at least one substituent independently selected from R11;R6, R7 and R8 are the same or different and are independently selectedfrom the group consisting of: hydrogen, 1-7C-alkyl, 3-7C-cycloalkyl, Ar,Har and Het, wherein each of said 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Harand Het is unsubstituted or substituted by at least one substituentindependently selected from R12; each R9 is independently selected fromthe group consisting of: hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl,wherein each of said 1-7C-alkyl and 3-7C-cycloalkyl is unsubstituted orsubstituted by at least one substituent independently selected from R12;each R10 is independently selected from the group consisting of:hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl; R11 is R5; each R12 isindependently selected from R5; each Ar is independently selected fromthe group consisting of phenyl and naphthyl; each Har is the same ordifferent and independently a fully aromatic or partially aromatic mono-or fused bicyclic ring or ring system, which contains at least oneheteroatom in the ring or ring system, made up of a first constituentbeing a 5- or 6-membered monocyclic unsaturated, aromatic heteroarylring A, which heteroaryl ring A comprises at least one heteroatomindependently selected from the group consisting of nitrogen, oxygen andsulfur, and, optionally, fused to said first constituent, a secondconstituent being a benzene ring, a 5-6C-cycloalkane ring, an additionalheteroaryl ring A or a heterocyclic ring B, wherein said Har is attachedvia a substitutable ring carbon or ring nitrogen atom of Har; each Hetis independently a fully saturated or partially unsaturated mono- orfused bicyclic ring or ring system made up of a first constituent beinga 3- to 7-membered monocyclic fully saturated or partially unsaturated,non-aromatic heterocyclic ring B, wherein the heterocyclic ring Bcomprises one to three heteroatoms independently selected from the groupconsisting of nitrogen, oxygen and sulfur, and which heterocyclic ring Bis optionally substituted by one or two oxo groups, and, optionally,fused to said first constituent, a second constituent being a benzogroup, any 3-7C-cycloalkane group or an additional heterocyclic ring B,wherein said Het ring or ring system is attached via a substitutablering carbon or ring nitrogen atom; Cyc is a group of formula A

in which G is a 5- or 6-membered saturated heterocyclic ring comprisingone or two heteroatoms independently selected from the group consistingof nitrogen, oxygen and sulfur, wherein said Cyc ring system is attachedvia a substitutable benzoring carbon atom; or a salt thereof.
 3. Acompound according to claim 1, which is selected from compounds formulaIa or Ib

in which Ra is —C(O)R1, in which R1 is 1-7C-alkyl, or imidazolo, or R1is 1-7C-alkyl which is substituted by one substituent selected from R5,or R1 is 2-4C-alkyl which is substituted by two hydroxyl groups ondifferent carbon atoms, or R1 is 2,2-dimethyl-[1,3]dioxolan-4-yl, or1-2C-alkyl which is substituted by 2,2-dimethyl-[1,3]dioxolan-4-yl; orin which Ra is —C(O)OR2, in which R2 is 1-7C-alkyl, 3-7C-cycloalkyl,phenyl, pyridyl, (1-4C-alkoxycarbonyl)-phenyl, or (1-4C-alkoxy)-phenyl,or R2 is 1-7C-alkyl which is substituted by one substituent selectedfrom R5, or R2 is 3-4C-alkyl which is substituted by two hydroxyl groupson different carbon atoms, or R2 is 1-2C-alkyl which is substituted by2,2-dimethyl-[1,3]dioxolan-4-yl; or in which Ra is —C(O)SR2, in which R2is 1-7C-alkyl, or R2 is 1-7C-alkyl which is substituted by onesubstituent selected from R5, or R2 is 3-4C-alkyl which is substitutedby two hydroxyl groups on different carbon atoms, or R2 is 1-2C-alkylwhich is substituted by 2,2-dimethyl-[1,3]dioxolan-4-yl; and in which Qis Rba- and/or Rbb- and/or Rbc-substituted phenyl, or Q is unsubstitutedphenyl, or Q is optionally substituted by Rca and/or Rcb, and is Har, orQ is Cyc; in which each R5 is independently selected from the groupconsisting of: 1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy,(1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkoxy, hydroxyl, 1-4C-alkylcarbonyloxy,phenoxy, phenyl-1-4C-alkoxy; 1-4C-alkoxycarbonyl, carboxyl, amino, mono-or di-1-4C-alkylamino, mono- or di-1-4C-alkylaminocarbonyl, carbamoyl,ureido, guanidino, 1-4C-alkylcarbonylamino, Het, Har and phenyl, whereineach of said Har or phenyl radicals alone or part of another group isunsubstituted or substituted by one or two substituents independentlyselected from the group consisting of halogen, 1-4C-alkoxy, nitro,trifluoromethyl, 1-4C-alkyl, 1-4C-alkoxycarbonyl and carboxyl, Rba ishalogen, 1-4C-alkyl, nitro, trifluoromethyl, 1-4C-alkoxy, mono- ordi-1-4C-alkylamino, hydroxyl, 1-4C-alkylcarbonyloxy, cyano, phenyl,morpholino, phenoxy, hydroxy-2-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy,3-7C-cycloalkoxy, 3-7C-cycloalkyl-1-4C-alkoxy, phenyl-1-4C-alkoxy,cyano-1-4C-alkoxy, or completely or predominantly fluorine-substituted1-4C-alkoxy, Rbb is 1-4C-alkoxy, halogen, trifluoromethyl or 1-4C-alkyl,Rbc is 1-4C-alkoxy, halogen, trifluoromethyl or 1-4C-alkyl, Rca ishalogen, 1-4C-alkyl, 1-4C-alkoxy, trifluoromethyl, phenyl, phenoxy ormorpholino, Rcb is halogen, 1-4C-alkyl or 1-4C-alkoxy, each Har isindependently a 5-membered monocyclic heteroaryl radical comprising one,two or three nitrogen atoms and/or one heteroatom independently selectedfrom the group consisting of oxygen and sulphur, or a 6-memberedmonocyclic heteroaryl radical comprising one or two nitrogen atoms, or a9-membered fused bicyclic heteroaryl radical comprising one, two orthree heteroatoms independently selected from the group consisting ofnitrogen, oxygen and sulphur, or a 10-membered fused bicyclic heteroarylradical comprising one, two or three heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen and sulphur, wherein saidHar is attached via a ring carbon atom or ring nitrogen atom of Har, Hetis morpholino, piperidino, pyrrolidino, 4N—H-piperazino,4N-(1-4C-alkyl)-piperazino, thiomorpholino, S-oxo-thiomorpholino orS,S-dioxo-thiomorpholino, Cyc is optionally substituted by halogen onits benzene ring, and is 1,3-benzodioxolyl,2,3-dihydro-1,4-benzodioxinyl, 2,2-difluoro-1,3-benzodioxolyl,2,2-dimethyl-1,3-benzodioxolyl, chromanyl, chromenyl or2,3-dihydro-benzofuranyl, wherein said Cyc ring system is attached via asubstitutable benzoring carbon atom; or a salt thereof.
 4. A compoundaccording to claim 1, which is from formula Ia

in which Ra is —C(O)R1, in which R1 is 1-5C-alkyl, or R1 is 1-4C-alkylwhich is mono-substituted by R5, in which R5 is 1-4C-alkoxy,1-4C-alkoxy-2-4C-alkoxy, (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkoxy,hydroxyl, pyridyl, pyrimidinyl, pyrazinyl, indolyl, thiazolyl, oxazolyl,1N-(1-4C-alkyl)-imidazolyl, 1N-(1-4C-alkyl)-pyrazolyl, phenyl,1-4C-alkoxycarbonyl, carboxyl, morpholino, di-1-4C-alkylaminocarbonyl,carbamoyl, ureido, guanidino, imidazolo, triazolo, pyrazolo or1-4C-alkylcarbonyloxy, or R1 is 3-4C-alkyl which is substituted by twohydroxyl groups on different carbon atoms, or R1 is 1-2C-alkyl which issubstituted by 2,2-dimethyl-[1,3]dioxolan-4-yl; or in which Ra is—C(O)OR2, in which R2 is 1-5C-alkyl, or R2 is 3-6C-cycloalkyl, phenyl,pyridyl, (1-4C-alkoxycarbonyl)-phenyl, or (1-4C-alkoxy)-phenyl, or R2 is1-4C-alkyl which is mono-substituted by R5, in which R5 is pyridyl,pyrimidinyl, pyrazinyl, 1N-(1-4C-alkyl)-imidazolyl,1N-(1-4C-alkyl)-pyrazolyl, phenyl, (1-4C-alkoxy)-phenyl,1-4C-alkoxycarbonyl, carboxyl, di-1-4C-alkylaminocarbonyl or carbamoyl,or R2 is 2-4C-alkyl which is mono-substituted by R5, in which R5 is1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy,(1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkoxy, hydroxyl, phenyl-1-4C-alkoxy,phenoxy, morpholino, piperidino, pyrrolidino,4N-(1-4C-alkyl)-piperazino, di-1-4C-alkylamino, imidazolo, triazolo,pyrazolo, 1-4C-alkylcarbonyloxy or 1-4C-alkylcarbonylamino, or R2 is3-4C-alkyl which is substituted by two hydroxyl groups on differentcarbon atoms, or R2 is 1-2C-alkyl which is substituted by2,2-dimethyl-[1,3]dioxolan-4-yl; or in which Ra is —C(O)SR2, in which R2is 1-5C-alkyl, or R2 is 2-4C-alkyl which is mono-substituted by R5, inwhich R5 is di-1-4C-alkylamino, hydroxyl or pyridyl; and in which Q isRba- and/or Rbb- and/or Rbc-substituted phenyl, or Q is unsubstitutedphenyl, or Q is substituted by Rca, and is thiophenyl, furanyl, pyridylor 1N-(methyl)-pyrazolyl, or Q is unsubstituted, and is thiophenyl,furanyl, pyridyl, 1N—(H)-pyrrolyl, 1N-(methyl)-pyrrolyl, benzothiophenylor benzofuranyl, or Q is 1,3-benzodioxol-5-yl, 1,3-benzodioxol-4-yl,2,3-dihydro-1,4-benzodioxin-5-yl, 2,3-dihydro-1,4-benzodioxin-6-yl,2,2-difluoro-1,3-benzodioxol-5-yl, 2,2-difluoro-1,3-benzodioxol-4-yl,2,3-dihydro-benzofuran-4-yl, 2,3-dihydro-benzofuran-5-yl,2,3-dihydro-benzofuran-6-yl or 2,3-dihydro-benzofuran-7-yl, or Q issubstituted by halogen on its benzene ring, and is 1,3-benzodioxol-5-yl,1,3-benzodioxol-4-yl, 2,3-dihydro-1,4-benzodioxin-5-yl,2,3-dihydro-1,4-benzodioxin-6-yl, 2,2-difluoro-1,3-benzodioxol-5-yl,2,2-difluoro-1,3-benzodioxol-4-yl, 2,3-dihydro-benzofuran-4-yl,2,3-dihydro-benzofuran-5-yl, 2,3-dihydro-benzofuran-6-yl or2,3-dihydro-benzofuran-7-yl; in which Rba is halogen, 1-4C-alkyl, nitro,trifluoromethyl, 1-4C-alkoxy, di-1-4C-alkylamino, hydroxyl,1-4C-alkylcarbonyloxy, cyano, phenyl, morpholino, phenoxy,hydroxy-2-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, or completely orpredominantly fluorine-substituted 1-4C-alkoxy, Rbb is 1-4C-alkoxy,halogen or 1-4C-alkyl, Rbc is 1-4C-alkoxy or halogen, Rca is halogen,1-4C-alkyl, 1-4C-alkoxy, phenyl, phenoxy or morpholino, or a saltthereof.
 5. A compound according to claim 1, which is from formula Ia

in which Ra is —C(O)R1, in which R1 is methyl, ethyl, propyl or butyl,or R1 is methyl which is mono-substituted by R5, ethyl which ismono-substituted by R5, or propyl which is mono-substituted by R5, inwhich R5 is methoxy, ethoxy, 2-methoxyethoxy,2-(2-methoxyethoxy)-ethoxy, hydroxyl, pyridyl, pyrimidinyl, pyrazinyl,indolyl, thiazolyl, oxazolyl, 1N-methyl-imidazolyl, 1N-methyl-pyrazolyl,phenyl, methoxycarbonyl, ethoxycarbonyl, carboxyl,dimethylaminocarbonyl, morpholino, carbamoyl, ureido, guanidino,imidazolo, triazolo, pyrazolo, ethylcarbonyloxy or methylcarbonyloxy, orR1 is propyl or butyl, each of which is substituted by two hydroxylgroups on different carbon atoms, or R1 is methyl or ethyl, each ofwhich is substituted by 2,2-dimethyl-[1,3]dioxolan-4-yl; or in which Rais —C(O)OR2, in which R2 is methyl, ethyl, propyl or butyl, or R2 iscyclohexyl, phenyl, pyridyl, (1-2C-alkoxycarbonyl)-phenyl, or(1-2C-alkoxy)-phenyl, or R2 is methyl which is mono-substituted by R5,ethyl which is mono-substituted by R5, or propyl which ismono-substituted by R5, in which R5 is pyridyl, pyrimidinyl, pyrazinyl,1N-methyl-imidazolyl, 1N-methyl-pyrazolyl, phenyl, (1-2C-alkoxy)-phenyl,methoxycarbonyl, ethoxycarbonyl, carboxyl, di-methylaminocarbonyl orcarbamoyl, or R2 is ethyl which is mono-substituted by R5, or propylwhich is mono-substituted by R5, in which R5 is methoxy, ethoxy,2-methoxyethoxy, 2-(2-methoxyethoxy)-ethoxy, hydroxyl, benzyloxy,phenoxy, morpholino, piperidino, pyrrolidino, 4N-(methyl)-piperazino,dimethylamino, imidazolo, triazolo, pyrazolo, methylcarbonyloxy,ethylcarbonyloxy, methylcarbonylamino or ethylcarbonylamino, or R2 ispropyl or butyl, each of which is substituted by two hydroxyl groups ondifferent carbon atoms, or R2 is methyl or ethyl, each of which issubstituted by 2,2-dimethyl-[1,3]dioxolan-4-yl; or in which Ra is—C(O)SR2, in which R2 is methyl, ethyl, propyl, butyl or pentyl, or R2is ethyl which is mono-substituted by R5, or propyl which ismono-substituted by R5, in which R5 is dimethylamino, hydroxyl orpyridyl; and in which Q is Rba- and/or Rbb- and/or Rbc-substitutedphenyl, or Q is unsubstituted phenyl, or Q is substituted by Rca, and isthiophenyl, furanyl, pyridyl or 1N-(methyl)-pyrazolyl, or Q isunsubstituted, and is thiophenyl, furanyl, pyridyl, 1N—(H)-pyrrolyl,1N-(methyl)-pyrrolyl, benzothiophenyl or benzofuranyl, or Q is1,3-benzodioxol-5-yl, 1,3-benzodioxol-4-yl,2,3-dihydro-1,4-benzodioxin-5-yl, 2,3-dihydro-1,4-benzodioxin-6-yl,2,2-difluoro-1,3-benzodioxol-5-yl, 2,2-difluoro-1,3-benzodioxol-4-yl,2,3-dihydro-benzofuran-4-yl, 2,3-dihydro-benzofuran-5-yl,2,3-dihydro-benzofuran-6-yl or 2,3-dihydro-benzofuran-7-yl, or Q issubstituted by bromine, chlorine or fluorine on its benzene ring, and is1,3-benzodioxol-5-yl, 1,3-benzodioxol-4-yl,2,3-dihydro-1,4-benzodioxin-5-yl, 2,3-dihydro-1,4-benzodioxin-6-yl,2,2-difluoro-1,3-benzodioxol-5-yl, 2,2-difluoro-1,3-benzodioxol-4-yl,2,3-dihydro-benzofuran-4-yl, 2,3-dihydro-benzofuran-5-yl,2,3-dihydro-benzofuran-6-yl or 2,3-dihydro-benzofuran-7-yl; in which Rbais chlorine, fluorine, bromine, methy, ethyl, methoxy, ethoxy,isopropyloxy, propoxy, hydroxyl, nitro, trifluoromethyl, dimethylamino,methylcarbonyloxy, cyano, phenyl, morpholino, phenoxy, 2-hydroxyethoxy,difluoromethoxy or trifluoromethoxy, Rbb is methoxy, ethoxy, fluorine,chlorine, bromine, ethyl or methyl, Rbc is methoxy, ethoxy, fluorine orchlorine, Rca is chlorine, fluorine, bromine, methyl, ethyl, methoxy,ethoxy, phenyl, phenoxy or morpholino, or a salt thereof.
 6. A compoundaccording to claim 1, which is from formula Ia

in which Ra is —C(O)R1, in which R1 is methyl, ethyl or propyl, or R1 ismethyl which is mono-substituted by R5, ethyl which is mono-substitutedby R5, or propyl which is mono-substituted by R5, in which R5 ismethoxy, 2-methoxyethoxy, hydroxyl, pyridyl, indolyl, phenyl,methoxycarbonyl, ethoxycarbonyl, dimethylaminocarbonyl, guanidino,imidazolo or methylcarbonyloxy; or in which Ra is —C(O)OR2, in which R2is methyl, ethyl, propyl or butyl, or R2 is cyclohexyl, phenyl, pyridyl,(methoxycarbonyl)-phenyl, or (methoxy)-phenyl, or R2 is methyl which ismono-substituted by R5, ethyl which is mono-substituted by R5, or propylwhich is mono-substituted by R5, in which R5 is pyridyl, phenyl,(methoxy)-phenyl, methoxycarbonyl or ethoxycarbonyl, or R2 is ethylwhich is mono-substituted by R5, or propyl which is mono-substituted byR5, in which R5 is methoxy, 2-methoxyethoxy, hydroxyl, benzyloxy,morpholino, pyrrolidino, 4N-(methyl)-piperazino, dimethylamino,imidazolo or methylcarbonylamino, or R2 is 2,3-dihydroxypropyl, or R2 is2,2-dimethyl-[1,3]dioxolan-4-yl-methyl; or in which Ra is —C(O)SR2, inwhich R2 is methyl, ethyl, propyl, butyl or pentyl, or R2 is ethyl whichis mono-substituted by R5, or propyl which is mono-substituted by R5, inwhich R5 is dimethylamino; and in which Q is Rba- and/or Rbb- and/orRbc-substituted phenyl, or Q is unsubstituted phenyl, or Q issubstituted by Rca, and is thiophenyl, furanyl or 1N-(methyl)-pyrazolyl,or Q is (morpholino)-pyridyl, or (phenoxy)-thiophenyl, or Q isunsubstituted, and is thiophenyl, furanyl, pyridyl, 1N—(H)-pyrrolyl,benzothiophenyl, 1N-(methyl)-pyrrolyl or benzofuranyl, or Q is1,3-benzodioxol-5-yl, 1,3-benzodioxol-4-yl,2,2-difluoro-1,3-benzodioxol-5-yl, 2,2-difluoro-1,3-benzodioxol-4-yl or2,3-dihydro-benzofuran-4-yl, or Q is substituted by bromine on itsbenzene ring, and is 1,3-benzodioxol-5-yl or 1,3-benzodioxol-4-yl; inwhich Rba is chlorine, fluorine, bromine, methy, ethyl, methoxy, ethoxy,isopropyloxy, propoxy, hydroxyl, nitro, trifluoromethyl, dimethylamino,methylcarbonyloxy, cyano, phenyl, morpholino, phenoxy, difluoromethoxyor trifluoromethoxy, Rbb is methoxy, ethoxy, fluorine, chlorine ormethyl, Rbc is fluorine, Rca is chlorine, methyl, ethyl or phenyl, or asalt thereof.
 7. A compound according to claim 1, which is a compound offormula Ia

in which Ra is —C(O)R1, in which R 1 is methyl, ethyl or propyl, or R1is methyl which is mono-substituted by R5, ethyl which ismono-substituted by R5, or propyl which is mono-substituted by R5, inwhich R5 is methoxy, ethoxy, 2-methoxyethoxy,2-(2-methoxyethoxy)-ethoxy, hydroxyl, pyridyl, pyrimidinyl, pyrazinyl,imidazolo, pyrazolo or methylcarbonyloxy, or R1 is 2,3-dihydroxy-propyl;or in which Ra is —C(O)0R2, in which R2 is methyl, ethyl or propyl, orR2 is methyl which is mono-substituted by R5, ethyl which ismono-substituted by R5, or propyl which is mono-substituted by R5, inwhich R5 is pyridyl, pyrazinyl or pyrimidinyl, or R2 is ethyl which ismono-substituted by R5, or propyl which is mono-substituted by R5, inwhich R5 is methoxy, ethoxy, 2-methoxyethoxy,2-(2-methoxyethoxy)-ethoxy, hydroxyl, imidazolo, pyrazolo ormethylcarbonyloxy, or R2 is 2,3-dihydroxy-propyl; or in which Ra is—C(O)SR2, in which R2 is methyl, ethyl or propyl, or R2 is methyl whichis mono-substituted by R5, ethyl which is mono-substituted by R5, orpropyl which is mono-substituted by R5, in which R5 is pyridyl orhydroxyl; and in which Q is Rba- and/or Rbb- and/or Rbc-substitutedphenyl, or Q is unsubstituted phenyl, or Q is substituted by Rca, and isthiophenyl or furanyl, or Q is unsubstituted, and is thiophenyl, furanylor pyridyl, or Q is 1,3-benzodioxol-5-yl, 1,3-benzodioxol-4-yl,2,2-difluoro-1,3-benzodioxol-5-yl or 2,2-difluoro-1,3-benzodioxol-4-yl;in which Rba is chlorine, fluorine, methy, ethyl, methoxy, ethoxy,difluoromethoxy or trifluoromethoxy, Rbb is methoxy, ethoxy, fluorine,chlorine or methyl, Rbc is fluorine, and Rca is chlorine, methyl orethyl, or a salt thereof.
 8. A compound according to claim 1, which is acompound of formula Ia

in which Ra is —C(O)R1, in which R1 is methyl, ethyl or propyl, or R1 is(R5)-methyl, 2-(R5)-ethyl, or 3-(R5)-propyl, in which R5 is methoxy,ethoxy, 2-methoxyethoxy, hydroxyl, imidazolo, pyridin-2-yl, pyridin-3-ylor pyridin-4-yl, or R1 is 2,3-dihydroxy-propyl; or in which Ra is—C(O)0R2, in which R2 is methyl, ethyl or propyl, or R2 is (R5)-methyl,2-(R5)-ethyl, or 3-(R5)-propyl, in which R5 is pyridin-2-yl,pyridin-3-yl or pyridin-4-yl, or R2 is 2-(R5)-ethyl, or 3-(R5)-propyl,in which R5 is methoxy, ethoxy, 2-methoxyethoxy, imidazolo or hydroxyl,or R2 is 2,3-dihydroxy-propyl; or in which Ra is —C(O)SR2, in which R2is methyl, ethyl or propyl, or R2 is (R5)-methyl, 2-(R5)-ethyl, or3-(R5)-propyl, in which R5 is pyridin-2-yl, pyridin-3-yl orpyridin-4-yl; and in which Q is 2-methoxyphenyl, 2-chlorophenyl,2-ethoxyphenyl or 2-methylphenyl, or Q is 2-(Rba)-3-(Rbb)-phenyl, inwhich Rba is chlorine, methoxy, ethoxy or methyl, Rbb is methoxy,chlorine, fluorine or methyl, or Q is 2-(Rba)-5-(Rbb)-phenyl, in whichRba is chlorine, methoxy, ethoxy or methyl, Rbb is methoxy, chlorine,fluorine or methyl, or Q is unsubstituted phenyl, or Q is unsubstituted,and is furan-2-yl, furan-3-yl or pyridin-3-yl, or Q is1,3-benzodioxol-4-yl or 2,2-difluoro-1,3-benzodioxol-4-yl; or a saltthereof.
 9. A compound according to claim 1, which is a compound offormula Ia

in which Ra is —C(O)R1, in which R1 is methyl, ethyl or propyl, or R1 ismethoxy-methyl, 2-methoxy-ethyl, (2-methoxyethoxy)-methyl,2-(2-methoxyethoxy)-ethyl, hydroxy-methyl, 2-hydroxy-ethyl,(pyridin-2-yl)-methyl, (pyridin-3-yl)-methyl, (pyridin-4-yl)-methyl,2-(pyridin-2-yl)-ethyl, 2-(pyridin-3-yl)-ethyl, or2-(pyridin-4-yl)-ethyl, or R1 is 2,3-dihydroxy-propyl; or in which Ra is—C(O)0R2, in which R2 is methyl, ethyl or propyl, or R2 is2-methoxy-ethyl, 2-(2-methoxyethoxy)-ethyl, 2-hydroxy-ethyl,(pyridin-2-yl)-methyl, (pyridin-3-yl)-methyl, (pyridin-4-yl)-methyl,2-(pyridin-2-yl)-ethyl, 2-(pyridin-3-yl)-ethyl, or2-(pyridin-4-yl)-ethyl, or R2 is 2,3-dihydroxy-propyl; or in which Ra is—C(O)SR2, in which R2 is methyl, ethyl or propyl; and in which Q is2-methoxyphenyl, or Q is 2-ethoxyphenyl, or Q is 2-(Rba)-3-(Rbb)-phenyl,in which Rba is methoxy or ethoxy, Rbb is methoxy or methyl, or Q is2-(Rba)-5-(Rbb)-phenyl, in which Rba is methoxy or ethoxy, Rbb ismethoxy or methyl, or Q is unsubstituted phenyl, or Q is unsubstituted,and is furan-2-yl, furan-3-yl or pyridin-3-yl, or Q is1,3-benzodioxol-4-yl; or a salt thereof.
 10. A compound according toclaim 1, which is a compound of formula Ia

in which Ra is —C(O)R1, in which R1 is methyl, ethyl or propyl, or R1 ismethoxy-methyl, 2-methoxy-ethyl, (2-methoxyethoxy)-methyl,2-(2-methoxyethoxy)-ethyl, hydroxy-methyl, 2-hydroxy-ethyl,(pyridin-2-yl)-methyl, (pyridin-3-yl)-methyl, (pyridin-4-yl)-methyl,2-(pyridin-2-yl)-ethyl, 2-(pyridin-3-yl)-ethyl, or2-(pyridin-4-yl)-ethyl, or R1 is 2,3-dihydroxy-propyl; or in which Ra is—C(O)0R2, in which R2 is methyl, ethyl or propyl, or R2 is2-methoxy-ethyl, 2-(2-methoxyethoxy)-ethyl, 2-hydroxy-ethyl,(pyridin-2-yl)-methyl, (pyridin-3-yl)-methyl, (pyridin-4-yl)-methyl,2-(pyridin-2-yl)-ethyl, 2-(pyridin-3-yl)-ethyl, or2-(pyridin-4-yl)-ethyl, or R2 is 2,3-dihydroxy-propyl; or in which Ra is—C(O)SR2, in which R2 is methyl, ethyl or propyl; and in which Q is2-ethoxyphenyl, or Q is 2-(Rba)-5-(Rbb)-phenyl, in which Rba is methoxy,Rbb is methoxy or methyl, or Q is 2-(Rba)-5-(Rbb)-phenyl, in which Rbais ethoxy, Rbb is methoxy or methyl; or a salt thereof.
 11. A compoundaccording to claim 2, which is a compound of formula Ia

in which Ra is —C(O)R1, in which R1 is methyl, ethyl, propyl or butyl,or Ra is —C(O)OR2, in which R2 is methyl, ethyl, propyl or butyl, or R2is benzyl or phenethyl, or R2 is phenyl or 3-methoxy-phenyl, or Ra is—C(O)SR2, in which R2 is ethyl; and Q is 2-chloro-phenyl,3-chloro-phenyl, 4-chloro-phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl,4-fluoro-phenyl, 2-trifluoromethyl-phenyl, 2-nitro-phenyl,3-nitro-phenyl,2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl,3-methoxy-phenyl, 4-methoxy-phenyl, 2,3-dimethoxy-phenyl, or2,4-dichloro-phenyl, or Q is phenyl, or Q is thiophenyl, furanyl, orpyridyl, or Q is 1,3-benzodioxolyl, 2,3-dihydro- 1,4-benzodioxinyl or2,3-dihydro-benzofuranyl; or a salt thereof.
 12. A compound according toclaim 2, which is a compound of formula Ia

in which Ra is —C(O)R1, in which R1 is 1-5C-alkyl, phenyl, pyridyl,morpholino, indolyl, or 1-5C-alkyl which is substituted by onesubstituent selected from R5, in which R5 is 1-4C-alkoxy, phenoxy,1-4C-alkoxy-2-4C-alkoxy, hydroxyl, benzyloxy, phenyl, pyridyl, indolyl,1-4C-alkoxycarbonyl, carboxyl, amino, di-1-4C-alkylamino, morpholino,piperidino, pyrrolidino, 4N-(1-4C-alkyl)-piperazin-1-yl,4N—(H)-piperazin-1-yl, carbamoyl, ureido, guanidino, imidazol-1-yl,1N-(H)-imidazol-4-yl, or 1N-(1-4C-alkyl)-imidazol-4-yl; or in which Rais —C(O)OR2, in which R2 is 1-5C-alkyl, phenyl, pyridyl, or(1-4C-alkoxy)-phenyl, or R2 is 1-5C-alkyl which is substituted by onesubstituent selected from R5, in which R5 is phenyl, pyridyl, indolyl,4-methyl-thiazolyl, 1-4C-alkoxycarbonyl, carboxyl, (1-4C-alkoxy)-phenyl,1N—(H)-imidazol-4-yl, or 1N-(1-4C-alkyl)-imidazol-4-yl, or R2 is2-5C-alkyl which is substituted by one substituent selected from R5, inwhich R5 is 1-4C-alkoxy, phenoxy, 1-4C-alkoxy-2-4C-alkoxy, hydroxyl,benzyloxy, 1-4C-alkylcarbonyloxy, amino, di-1-4C-alkylamino,1-4C-alkylcarbonylamino, morpholino, piperidino, pyrrolidino,4N-(1-4C-alkyl)-piperazin-1-yl, 4N—(H)-piperazin-1-yl, or imidazol-1-yl;or in which Ra is —C(O)SR2, in which R2 is 1-5C-alkyl, or 2-5C-alkylwhich is substituted by one substituent selected from R5, in which R5 is1-4C-alkoxycarbonyl, carboxyl, hydroxyl, 1-4C-alkylcarbonyloxy,di-1-4C-alkylamino, 1-4C-alkylcarbonylamino, pyridyl or pyrazinyl; andin which Q is Rba- and/or Rbb- and/or Rbc-substituted phenyl, in whichRba is halogen, 1-4C-alkyl, nitro, trifluoromethyl, or 1-4C-alkoxy, Rbbis 1-4C-alkoxy, or halogen, Rbc is 1-4C-alkoxy, or Q is Rba- andRbb-substituted phenyl, in which Rba is 1-4C-alkoxy, or halogen, Rbb is1-4C-alkoxy, or halogen, or a salt thereof.
 13. A compound according toclaim 2, which is a compound of formula Ia

in which, Ra is —C(O)R1, in which R1 is methyl or propyl; or in which Rais —C(O)OR2, in which R2 is methyl, ethyl, butyl, phenethyl or3-methoxy-phenyl; or in which, Ra is —C(O)SR2, in which R2 is ethyl; andin which Q is 2-chloro-phenyl, 3-chloro-phenyl, 3-fluoro-phenyl,2-trifluoromethyl-phenyl, 2-nitro-phenyl, 3-nitro-phenyl,2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-methoxy-phenyl,4-methoxy-phenyl, 2,3-dimethoxy-phenyl, or 2,4-dichloro-phenyl, or Q isphenyl, or Q is thiophen-2-yl, thiophen-3-yl, furan-2-yl, furan-3-yl orpyridin-3-yl, or Q is 1,3-benzodioxol-5-yl; or a salt thereof.
 14. Acompound according to claim 1, in which Ra is —C(O)OR2, in which R2 isethyl; or a salt thereof.
 15. A compound according to claim 1, which isa compound of formula Ia

in which Q is unsubstituted, and is phenyl or furanyl, thiophenyl orpyridyl, or a salt thereof.
 16. A compound according to claim 1, whichis a compound of formula Ia

in which Q is 2-ethoxy-phenyl, or a salt thereof.
 17. A pharmaceuticalcomposition comprising one or more compounds according to claim 1, or apharmaceutically acceptable salt thereof, together with apharmaceutically acceptable excipient and/or vehicle.
 18. A compound offormula I according to claim 1, wherein Rba, Rbb and Rbc are the same ordifferent and are independently selected from the group consisting of1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har, Het, halogen, trifluoromethyl,nitro, cyano, guanidino, amidino, —C(O)R6, —C(O)OR7, —C(O)N(R8)R9,—N(R10)C(O)R6, —N(R 10)C(O)OR7, —N(R10)C(O)N(R8)R9, —N(R10)S(O)₂R6,—N(R10)S(O)₂N(R8)R9, —OC(O)R6, —OC(O)N(R8)R9, —OR7, —N(R8)R9 and —SR7,wherein each of said 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het isunsubstituted or substituted by at least one substituent independentlyselected from R11.
 19. A compound of formula I

wherein Ra is —C(O)R1, —C(O)OR2, —C(O)SR2, —C(O)N(R3)R4, —S(O)₂R1, or—S(O)₂N(R3)R4; Rb is Q-2-4C-alkenyl, in which Q is optionallysubstituted by Rba and/or Rbb and/or Rbc, and is phenyl or naphthyl, orQ is optionally substituted by Rca and/or Rcb, and is Har, or Q is Cyc;in which R1, R2 and R3 are the same or different and are independentlyselected from the group consisting of: hydrogen, 1-7C-alkyl,3-7C-cycloalkyl, Ar, Har and Het, wherein each of said 1-7C-alkyl,3-7C-cycloalkyl, Ar, Har and Het is unsubstituted or substituted by atleast one substituent independently selected from R5; each R4 isindependently selected from the group consisting of: hydrogen,1-7C-alkyl and 3-7C-cycloalkyl, wherein each of said 1-7C-alkyl and3-7C-cycloalkyl is unsubstituted or substituted by at least onesubstituent independently selected from R5; R5, Rba, Rbb, Rbc, Rca andRcb are the same or different and are independently selected from thegroup consisting of: 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har, Het, halogen,trifluoromethyl, nitro, cyano, guanidino, amidino, —C(O)R6, —C(O)OR7,—C(O)N(R8)R9, —S(O)₂R6, —S(O)₂N(R8)R9, —N(R10)C(O)R6, —N(R10)C(O)OR7,—N(R10)C(O)N(R8)R9, —N(R10)S(O)₂R6, —N(R10)S(O)₂N(R8)R9, —OC(O)R6,—OC(O)N(R8)R9, —OR7, —N(R8)R9 and —SR7, wherein each of said 1-7C-alkyl,3-7C-cycloalkyl, Ar, Har and Het is unsubstituted or substituted by atleast one substituent independently selected from R11; R6, R7 and R8 arethe same or different and are independently selected from the groupconsisting of: hydrogen, 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het,wherein each of said 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het isunsubstituted or substituted by at least one substituent independentlyselected from R12; each R9 is independently selected from the groupconsisting of: hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl, wherein each ofsaid 1-7C-alkyl and 3-7C-cycloalkyl is unsubstituted or substituted byat least one substituent independently selected from R12; each R10 isindependently selected from the group consisting of: hydrogen,1-7C-alkyl and 3-7C-cycloalkyl; R11 is R5; each R12 is independentlyselected from R5; each Ar is independently selected from the groupconsisting of phenyl and naphthyl; each Har is the same or different andindependently a fully aromatic or partially aromatic mono- or fusedbicyclic ring or ring system, which contains at least one heteroatom inthe ring or ring system, made up of a first constituent being a 5- or6-membered monocyclic unsaturated, aromatic heteroaryl ring A, whichheteroaryl ring A comprises at least one heteroatom independentlyselected from the group consisting of nitrogen, oxygen and sulfur, and,optionally, fused to said first constituent, a second constituent beinga benzene ring, a 5-6C-cycloalkane ring, an additional heteroaryl ringA, or a heterocyclic ring B, wherein said Har is attached via asubstitutable ring carbon or ring nitrogen atom of Har; each Het isindependently a fully saturated or partially unsaturated mono- or fusedbicyclic ring or ring system made up of a first constituent being a 3-to 7-membered monocyclic fully saturated or partially unsaturated,non-aromatic heterocyclic ring B, wherein the heterocyclic ring Bcomprises one to three heteroatoms independently selected from the groupconsisting of nitrogen, oxygen and sulfur, and which heterocyclic ring Bis optionally substituted by one or two oxo groups, and, optionally,fused to said first constituent, a second constituent being a benzogroup, a 3-7C-cycloalkane group, or an additional heterocyclic ring B,wherein said Het ring or ring system is attached via a substitutablering carbon or ring nitrogen atom; Cyc is optionally substituted byhalogen on its benzene ring, and is a group of formula A

in which G is optionally substituted by Rda and/or Rdb, and is a 5- or6-membered saturated heterocyclic ring comprising one or two heteroatomsindependently selected from the group consisting of nitrogen, oxygen andsulfur, in which Rda is 1-4C-alkyl or halogen, Rdb is 1-4C-alkyl orhalogen, wherein said Cyc ring system is attached via a substitutablebenzoring carbon atom.
 20. A salt of a compound of formula I

wherein Ra is —C(O)R1, —C(O)OR2, —C(O)SR2, —C(O)N(R3)R4, —S(O)₂R1, or—S(O)₂N(R3)R4; Rb is Q-2-4C-alkenyl, in which Q is optionallysubstituted by Rba and/or Rbb and/or Rbc, and is phenyl or naphthyl, orQ is optionally substituted by Rca and/or Rcb, and is Har, or Q is Cyc;in which R1, R2 and R3 are the same or different and are independentlyselected from the group consisting of: hydrogen, 1-7C-alkyl,3-7C-cycloalkyl, Ar, Har and Het, wherein each of said 1-7C-alkyl,3-7C-cycloalkyl, Ar, Har and Het is unsubstituted or substituted by atleast one substituent independently selected from R5; each R4 isindependently selected from the group consisting of: hydrogen,1-7C-alkyl and 3-7C-cycloalkyl, wherein each of said 1-7C-alkyl and3-7C-cycloalkyl is unsubstituted or substituted by at least onesubstituent independently selected from R5; R5, Rba, Rbb, Rbc, Rca andRcb are the same or different and are independently selected from thegroup consisting of: 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har, Het, halogen,trifluoromethyl, nitro, cyano, guanidino, amidino, —C(O)R6, —C(O)OR7,—C(O)N(R8)R9, —S(O)₂R6, —S(O)₂N(R8)R9, —N(R10)C(O)R6, —N(R10)C(O)OR7,—N(R10)C(O)N(R8)R9, —N(R10)S(O)₂R6, —N(R10)S(O)₂N(R8)R9, —OC(O)R6,—OC(O)N(R8)R9, —OR7, —N(R8)R9 and —SR7, wherein each of said 1-7C-alkyl,3-7C-cycloalkyl, Ar, Har and Het is unsubstituted or substituted by atleast one substituent independently selected from R11; R6, R7 and R8 arethe same or different and are independently selected from the groupconsisting of: hydrogen, 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het,wherein each of said 1-7C-alkyl, 3-7C-cycloalkyl, Ar, Har and Het isunsubstituted or substituted by at least one substituent independentlyselected from R12; each R9 is independently selected from the groupconsisting of: hydrogen, 1-7C-alkyl and 3-7C-cycloalkyl, wherein each ofsaid 1-7C-alkyl and 3-7C-cycloalkyl is unsubstituted or substituted byat least one substituent independently selected from R12; each R10 isindependently selected from the group consisting of: hydrogen,1-7C-alkyl and 3-7C-cycloalkyl; R11 is R5; each R12 is independentlyselected from R5; each Ar is independently selected from the groupconsisting of phenyl and naphthyl; each Har is the same or different andindependently a fully aromatic or partially aromatic mono- or fusedbicyclic ring or ring system, which contains at least one heteroatom inthe ring or ring system, made up of a first constituent being a 5- or6-membered monocyclic unsaturated, aromatic heteroaryl ring A, whichheteroaryl ring A comprises at least one heteroatom independentlyselected from the group consisting of nitrogen, oxygen and sulfur, and,optionally, fused to said first constituent, a second constituent beinga benzene ring, a 5-6C-cycloalkane ring, an additional heteroaryl ringA, or a heterocyclic ring B, wherein said Har is attached via asubstitutable ring carbon or ring nitrogen atom of Har; each Het isindependently a fully saturated or partially unsaturated mono- or fusedbicyclic ring or ring system made up of a first constituent being a 3-to 7-membered monocyclic fully saturated or partially unsaturated,non-aromatic heterocyclic ring B, wherein the heterocyclic ring Bcomprises one to three heteroatoms independently selected from the groupconsisting of nitrogen, oxygen and sulfur, and which heterocyclic ring Bis optionally substituted by one or two oxo groups, and, optionally,fused to said first constituent, a second constituent being a benzogroup, a 3-7C-cycloalkane group, or an additional heterocyclic ring B,wherein said Het ring or ring system is attached via a substitutablering carbon or ring nitrogen atom; Cyc is optionally substituted byhalogen on its benzene ring, and is a group of formula A

in which G is optionally substituted by Rda and/or Rdb, and is a 5- or6-membered saturated heterocyclic ring comprising one or two heteroatomsindependently selected from the group consisting of nitrogen, oxygen andsulfur, in which Rda is 1-4C-alkyl or halogen, Rdb is 1-4C-alkyl orhalogen, wherein said Cyc ring system is attached via a substitutablebenzoring carbon atom.
 21. A pharmaceutical composition comprising oneor more compounds according to claim 2, or a pharmaceutically acceptablesalt thereof, together with a pharmaceutically acceptable excipientand/or vehicle.
 22. A pharmaceutical composition comprising one or morecompounds according to claim 3, or a pharmaceutically acceptable saltthereof, together with a pharmaceutically acceptable excipient and/orvehicle.
 23. A compound of formula I according to claim 1, wherein Q isoptionally substituted by Rba and/or Rbb and/or Rbc, and is phenyl ornaphthyl.
 24. A compound of formula I according to claim 1, wherein Q isoptionally substituted by Rca and/or Rcb, and is Har.
 25. A compound offormula I according to claim 1, wherein Q isCyc.